Dr. Geert Vanden Bossche
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ASSOCIATIONS
Dr. Robert Wallace Malone (born 1959) ( Dr. Robert Malone has said in 2021 and 2022 that Dr. Vanden Bossche was his "partner" in raising awareness of risks of strengthening pathogens when vaccinating during a pandemic. )
About
Creative thinker, innovator, entrepreneur and problem solver always open to new consultancy or career opportunities in the field of Vaccines, Life Sciences and/ or Global Health to deliver solutions to unmet medical needs. My work and supportive advice are driven by a relentless passion to help bridge the gap between research and enterprise and to translate scientific breakthrough findings into competitive vaccine products. I strongly believe that a well-balanced synergy between multiple scientific disciplines combined with sound strategic insights and dedicated managerial support is critical to solving complex challenges in Human and Animal Health.
Profile: Experienced management professional; expert in vaccine R&D and early vaccine dvpt,; proficiency in program and grant management; used to working in a heavily interconnected environment (in private and nonprofit sector) while managing the needs of numerous stakeholders. Proven track record of success in designing and developing vaccines, managing dynamic, high-performing consortia, developing efficient processes to deliver impact, offering expert scientific-technical advice on complex immunisation projects, leading vaccine R&D work as CSO. Proficiency in program management, team leadership, patent writing, laboratory research, immunology, epidemiology, microbiology, vaccine technologies, preclinical vaccine dvpt. Substantial experience in strategic budgeting, CMC- and IP-related matters, incl. patent infringement and litigations. Over 2 decades of professional experience working in Europe and the US in managing implementation of immune interventions to address unmet medical needs. Highly familiar with major challenges in Global Health (as previously engaged with B. & M. Gates Foundation and GAVI).
I am particularly interested in engaging with international companies or organisations in the private or public sector or which are involved in public-private partnerships targeted at translational medicine programs, preferably in the field of Vaccine Innovation or Intellectual Property (e.g., IP issues, litigations related to infringement of vaccine patents).
Experience
- VARECO
Managing Director ( Sep 2012 – 2019 / Employment Duration : 7 yrs )
Location : Europe
Independent vaccine consultant with a long- standing track record in Academia, Vaccine Industry and Global Health (GH); providing support on vaccine project management as well as advice, guidance and expert opinion on preclinical development of vaccines & biologicals, from project selection up to IND.
Assignments include prophylactic and therapeutic vaccine projects in Human and Veterinary Vaccine Industry, Small Biotech, Global Health organizations in the US or Europe
My knowledge, insights and skills cover a diversified spectrum of Life Science domains including:
Life Science Project Management (in early and late dvpt)
Due diligence on technologies & processes related to vaccines, adjuvants and biologicals
Patent writing and strategic IP management
Guidance on regulatory requirements to CMC documentation, DMF files
Target product profiling and SWOT analysis
Infectious and immune-mediated diseases including their (immune) pathogenesis and epidemiology
Host-pathogen interactions and mechanisms of immune escape
Innate and adaptive immunology (both, humoral and cell-mediated)
Antigen discovery
Preclinical vaccine development (including animal experimentation as well as immunological and physicochemical characterization of vaccines and biologicals)
Vaccine formulation science and modern vaccine delivery technologies (incl. devices); modern technologies for enhancement of antimicrobicidal activity in multidose vaccines
Small-scale pre-GMP vaccine manufacturing (incl. synthetic chemistry of Ag or adjuvant, recombinant Ag expression, viral vectors, upstream and downstream processing)
To enhance the quality and capacity of my consultancy services, I leverage an extensive network of professional contacts providing direct access to US and European governmental and regulatory agencies, Academia and Research Institutions, Human and Veterinary Vaccine Industry, Global & Public Health organizations and CROs in the US and Europe.
- German Centre for Infection Research (DZIF)
Head of the Vaccine Development Office ( Aug 2017 – Dec 2017 / Employment Duration : 5 mos )
Location : Cologne, Germany
Spearheading a portfolio of translational vaccine research projects, conducted at German universities and research centres sponsored by DZIF. Holding overall accountability for strategic alignment of translational infection research in support of preclinical and early clinical testing.
Developing a trans-academic translational network for Vaccine development totalling eight universities and research organizations across Germany.
- Univac
Chief Innovation & Scientific Officer ( Nov 2014 – Nov 2016 / Employment Duration : 2 yrs 1 mo )
Location : Huldenberg
II founded Univac as inventor of a new vaccine technology which I subsequently further developed as CSO of the Company. The technology enables the development of universal vaccines educating the host immune system to redirect immune targeting away from canonical antigens to a widely divergent spectrum of vitally vulnerable pathogen-derived ‘self-mimicking’ antigens, irrespective of MHC polymorphism. Although ‘non-self’ and exposed on the surface of infected or pathologically altered cells, these antigens are not effectively recognised upon natural infection or disease.
This new type of vaccines harnesses the power of the immune system by unlocking the untapped potential of self-centered Natural Killer (NK) cells capable of recognising these unconventional antigens. The resulting type of immune response is unprecedented and licenses the host immune system to readily eliminate infection or to cure disease across a broad range of unrelated pathogens and/ or mammalian species. This sharply contrasts with conventional targeting of natural immune responses as induced by conventional vaccines.
Because of their fast (NK cells) and universally protective effect, Univac vaccines are uniquely suited to prevent pathogenic agents from escaping host immune responses as of an early stage of infection or immune-mediated disease. The technology obviates the need for traditional adjuvants, multiple boost injections or expensive manufacturing processes and is readily compatible with intradermal or mucosal administration. Hence, it also offers unprecedented advantages in terms of safety, convenience and cost-effectiveness.
- Global Alliance for Vaccines and Immunisation (GAVI)
Program Manager ( Mar 2015 – Mar 2016 / Employment Duration : 1 yr 1 mo )
Location : Geneva Area, Switzerland
During my term at GAVI, I coordinated GAVI’s Ebola Vaccine Program and contributed to the implementation of an integrated vaccine work plan in collaboration with Global Health Partners (WHO, Bill & Melinda Gates Foundation, CDC, UNICEF), regulators (FDA) and vaccine manufacturers to enable timely deployment or stockpiling of Ebola vaccine candidate(s) that suitably meet the requirements for use in an Ebola epidemic. In this capacity, I also contributed to several workshops aimed at proposing novel and efficient approaches to improving preparedness in cases of Global Health Emergencies of international concern.
- Positions in Academia
DVM, PhD, adjunct professor ( Sep 1980 – Sep 2015 / Employment Duration : 35 yrs 1 mo )
Training in Veterinary Medicine at the faculty Notre-Dame-de-la-Paix and the State University of Ghent (1980-1983)
Doctoral degree in Veterinary Medicine from State University of Ghent (1983)
Postdoctoral training in Equine Medicine and Surgery at the Free University of Berlin, Germany (1984-1987)
Postdoctoral Fellowship in Virology at James A. Baker Institute for Animal Health, Cornell University, Ithaca, NY 14850, USA (Sept 1990- mid 1991)
Research scientist in Virology, Immunology and Molecular Biology at the Robert Koch Institute in Berlin, Germany (1987- 1990)
Board certified in Veterinary Virology (1990)
Senior Research Scientist and Head of Environmental Virology at University of Hohenheim, Stuttgart, Germany (1990-1994)
Board certified in Veterinary Microbiology and Animal Hygiene (1992)
Visiting Professor in Environmental Virology at the European Faculty for Environmental Sanitation (1998-2004)
Adjunct Professor in Environmental Virology and Zoonotic Diseases at University of Hohenheim, Stuttgart, Germany (1997-2000)
Visiting Scientist at the REGA Institute, KU Leuven, Belgium (2013 - 2015)
- [ July 2011 - Oct 2014 : VaReCo]
- Bill & Melinda Gates Foundation (BMGF)
Senior Program Officer, Global Health, Vaccine Discovery ( May 2008 – Jun 2011 / Employment Duration : 3 yrs 2 mos )
Location : Seattle, Washington 98102, USA
Responsible for operating Vaccine Programs (e.g., HIV-1, Malaria, TB, Polio...) and establishing international product development partnerships for immune interventions in Global Health (e.g., with Academia, Biotech Industry, NIH, Welcome Trust, WHO, PATH). Coordinating and spearheading international collaborations and consortia on innovative vaccine approaches and steering multidisciplinary vaccine initiatives
- Solvay Biologicals
Global Project Director Influenza Vaccines ( Jul 2007 – May 2008 / Employment Duration : 11 mos )
Location : Weesp, the Netherlands
Responsible for leading the operational aspects of an interdisciplinary project team including the planning and implementation of adjuvanted Influenza vaccines that enable dose sparing.
Implementation of commercial-scale production of cell-based methods and expansion of Influenza vaccine production capacity such as to meet DHSS (U.S. Department of Human Health Services) contractual requirements (Pandemic Influenza Preparedness Plan)
[ 2006 - Solvay - Bioterror .. https://www.newspapers.com/image/423097744 / https://www.newspapers.com/image/423097804/?terms=solvay%20pharmaceuticals&match=1 ]
[ US congress - 250 million to SOlvay to speed up vaccine production .. 2006 .. https://www.newspapers.com/image/452709701/?terms=solvay%20pharmaceuticals&match=2 ]
[ Solvay 2007 article - https://www.newspapers.com/image/631581164/?terms=solvay%20pharmaceuticals&match=1 - genetically engineered univ. flu vaccine ... even mentions Protein Sciences ... of Meriden CT ... ]
[ 2007 - Earl E. Sands .. https://www.newspapers.com/image/423230491/?terms=solvay%20pharmaceuticals&match=1 .. }
[ https://www.newspapers.com/image/475829693/?terms=solvay%20pharmaceuticals&match=1 ... male menopause ... ]
[ FOurnier .. https://www.newspapers.com/image/164567728/?terms=solvay%20pharmaceuticals&match=1 .. .Solvay... Marietta Georgia .. ]
2008 : https://www.newspapers.com/image/422778322/?terms=solvay%20pharmaceuticals&match=1
Fluvoxamine (which may help tread covid) is from Solvay .. https://www.newspapers.com/image/298932933/?terms=solvay%20pharmaceuticals&match=1 / https://www.covid19treatmentguidelines.nih.gov/therapies/immunomodulators/fluvoxamine/
Sep 2009 : Solvay Biologicals may start cell-based vaccine production in Weesp, Netherlands. : https://www.thefreelibrary.com/Solvay+Biologicals+may+start+cell-based+vaccine+production+in+Weesp%2C...-a0209173511 ]
[see Solvay and UPMC .. .below...]
- Novartis Vaccines & Diagnostics
Director, Research Program Leader and Head of Adjuvants ( Aug 2006 – Jul 2007 / Employment Duration : 1 yr )
Location : Siena, Italy & Emeryville, USA
Vaccine Research Program/Adjuvant Program responsibilities:
Project leader of NVD's RSV vaccine project (Respiratory Syncytial Virus)
Coordinator of preclinical activities on combined seasonal RSV-Influenza vaccine for elderly & high risk adults
Responsible for defining and shaping the scope and strategy of NVD's adjuvant and vaccine delivery technologies including management of NVD’s adjuvant portfolio, opportunity sourcing, and establishment of an internal interdisciplinary due diligence team for the evaluation of relevant extramural opportunities.
- GlaxoSmithKline Biologicals
Head of Adjuvant Technologies and Alternative Deliveries, R&D ( May 2001 – May 2006 / Employment Duration : 5 yrs 1 mo )
Location : Rixensart, Belgium
Research Program Leader on Vaccine Formulation Development & Alternative Deliveries and in charge of biophysical characterization activities on adjuvanted vaccine formulations.
Coordination and follow-up of extramural contracts & collaboration agreements on new immunization strategies and innovative vaccine adjuvant, delivery or formulation technologies (e.g., co-delivery, mucosal, subcutaneous, intradermal immunization)
Development and validation of vaccine and adjuvant characterization assays
Study of adjuvant-antigen interaction and of adjuvant structure-function relationship
Coordination and resource management of preclinical activities including CMC section of INDs and cGMP production of (adjuvanted) vaccine candidates
Planning laboratory activities and establishing outside collaborations with academia
- GSK Biologicals
Senior Project Leader ‘Adolescent Vaccine Projects' ( Jun 1998 – May 2001 / Employment Duration : 3 yrs )
Location : Rixensart, Belgium
Project Management on Raw Material Traceability (RAMATRA) and vaccine projects in Late Development, e.g., Herpes Simplex Virus type 2, Hepatitis B, Streptococcus Pneumoniae and Enterotoxic Escherichia Coli (in collaboration with SBL Vaccines, Sweden)
New Biotech Vaccine Development and QC-QA Manager ( Feb 1995 – May 1998 / Employment Duration : 3 yrs 4 mos )
Location : Rixensart, Belgium
Major responsibilities (3 direct reports; 6 technicians):
Management and coordination of vaccine product development, optimization as well as validation of analytical methods in accordance with regulatory requirements or guidelines and vaccine marketing constraints
Budget management of all activities related to QC assay development
Transfer from R&D and further development of new QC-relevant characterization techniques on new vaccine candidates (e.g., HSV-2 vaccine, Lyme disease vaccine); contacts with national/ international regulatory and health authorities (e.g., FDA, NIBSC, IHE, WHO,…) on technical dossiers; active participation in pre-IND meetings
No mention of Cornell under Education
2021-09-25-linkedin-com-geertvandenbossche-img-1-education.jpg
https://drive.google.com/file/d/1UrOVTkbE0NeKZLpgunWw0KvLT2zq_DG3/view?usp=sharing
https://www.nature.com/articles/ni1109-1133
Lessons learned. Nat Immunol 10, 1133 (2009). https://doi.org/10.1038/ni1109-1133
Issue Date
November 2009
DOI
Lessons learned"
Nature Immunology volume 10, page 1133 (2009)Cite this article
524 Accesses2 CitationsMetrics detailsAdditional work is needed to prepare for the next pandemic viral outbreak.
Largely thanks to lessons learned from previous recent pandemic scares, including the H5N1 'bird flu', governments around the world responded in an efficient manner to the initial outbreak of H1N1. In addition, the good news that one vaccine dose, rather than two doses, is sufficient to protect adults has alleviated some anxiety about H1N1 vaccine availability and has allowed the United States and seven other rich nations to pledge to donate portions of their vaccine supply to poorer countries unable to purchase doses sufficient to protect their vulnerable populations.
However, the fact remains that it will be impossible to produce and administer enough vaccine doses in time to vaccinate the susceptible population—even in some wealthy nations, including the United States—before the anticipated peak of the autumn H1N1 flu pandemic. In addition, not enough is known about several parameters crucial to determining if the available vaccine supplies can be stretched.
Although governments around the globe signed contracts to buy H1N1 vaccine from 20 different companies shortly after the start of the H1N1 outbreak this past summer, vaccine production has been delayed by several factors. Many companies, including all five contracted by the United States, are using the tried-and-true but slow method of growing live virus in chicken eggs. For as-yet-unknown reasons, the reference 'seed strain' of H1N1 has been growing at a pace even slower than anticipated. In addition, companies all over the world were forced to divide their production capacity among vaccines protecting against H1N1 and those designed to combat seasonal flu. Clearly, to circumvent such obstacles during future efforts to combat pandemic viruses, new methods of growing virus must be explored, and efforts to approve and 'scale up' these methods must be expedited.
In an encouraging development, the Belgian vaccine maker Solvay Biologicals just received approval from the Dutch government to produce seasonal and H1N1 influenza vaccines in its cell culture manufacturing facility in the Dutch city of Weesp. In addition, the virus-like particle-based influenza vaccine developed by Novavax has shown promising efficacy results in mid-stage trials. Governmental regulatory agencies should make an effort to expedite the assessment and approval of safe and effective cell culture–based influenza vaccines and to accelerate the construction of facilities needed to produce these vaccines in large quantities. For example, governments should give serious consideration to funding proposals like the University of Pittsburgh Medical Center's 21st Century Biodefense Center, a facility that would augment and speed up vaccine production and development and operate as a public-private partnership.
Even if vaccines are available in abundance, safely and effectively administering them to susceptible people located in developing regions scarce in refrigerators and hypodermic needles can present an enormous challenge. Fortunately, clever researchers are devising ways to circumvent the need for refrigerators and needles while simultaneously boosting the effectiveness of vaccines. For example, although it has been tested only on animals thus far, a steel patch 'decorated' with an array of needles can be coated with a thickened, dry form of a liquid vaccine. In addition to being resistant to high temperatures, this patch can, in theory, be self-administered. Another bonus is that the short length of the needles facilitates delivery of the vaccine to the skin, a site much richer in antigen-presenting cells than the muscle targeted by traditional needles. Public and private funding bodies should target and support this type of research.
More knowledge about strategies for stretching limited vaccine supplies would also increase preparedness for future viral pandemics. For example, adjuvants can boost the amplitude, quality and/or duration of immune responses to many vaccines. However, exactly how adjuvants work is not understood, and some adjuvant-containing vaccines have been associated with deadly, albeit rare, side effects. As a result, some countries, including the United States, have refrained from including adjuvants in influenza vaccines. More research into how adjuvants actually influence the human immune system might help unravel the mystery surrounding these substances, make governments more willing to use them to stretch the supply of vaccines during future viral pandemics and aid efforts to rationally design newer, better adjuvants. In an encouraging turn of events, the US National Institute for Allergy and Infectious Disease has begun soliciting applications for grants aimed at profiling human immune systems at rest and after vaccination and/or infection.
Knowing precisely which susceptible populations to vaccinate first can also help stretch the population-wide effectiveness, if not the actual quantity, of limited vaccine supplies. Fortunately, epidemiology and public health researchers are using new methods, including mathematical modeling, to determine if the existing strategy of first vaccinating the most susceptible people (usually the elderly, infants and pregnant women) is really the most effective way to stop the spread of a virus. For example, data published in Science indicate an alternative strategy of prioritizing children (who spread the virus among themselves in school) and their parents (who act as conduits, carrying the virus from their children to the rest of society) for vaccination more efficiently combats viral spread and death due to viral infection. Governments and health providers need to stay abreast of and promote (for example, with more funding and facilities) this research and should rigorously explore the possibility of incorporating these findings into recommended vaccination strategies.
Deficiencies revealed during the worldwide response to the H1N1 outbreak must be remembered by governments, regulatory agencies, health providers and researchers long after this flu season ends. Efforts to remove obstacles to readiness need to be made before the next viral outbreak occurs.
Professional Experience
March 2018-Present Countering Immune Evasion Independent Researcher Design and develop NK cell-based vaccines inducing universally and broadly protective immune responses to infectious pathogens and other, non-infectious immune subversive agents (in collaboration with Academia and Industry).Aug 2017-Dec 20172012-Aug 2019German Center for Infection Research (DZIF) at the University Hospital of CologneHead of the Vaccine Development Office Coordinating and managing a portfolio of translational vaccine research projects conducted at German universities and research centers sponsored by DZIF. Responsible for strategic alignment of translational infection research.VaReCo (Vaccine Research and Collaborations)Managing Director Providing scientific advice to vaccine biotech and Animal Health companies as well as to nonprofit organizations (e.g., GAVI, PATH, Bill & Melinda Gates Foundation, GALVmed, NIH, WHO, Academia) on health interventions, immunology-, vaccine-and adjuvant-related matters and nutraceuticals. Expert witness on vaccine-related litigationsMid 2011-End 2017UNIVAC llc (USA) and UNIVAC NV (BE)CSO Initiating, coordinating and implementing all vaccine R&D work in collaboration with external partners (Company focus: Universal, NK cell-based vaccines & innovative approaches to immune intervention in veterinary and human infectious and immune-mediated diseases)Mid 2015-Mid 2016GLOBAL ALLIANCE FOR VACCINES AND IMMUNIZATION (GAVI),Geneva, SwitzerlandEbola Vaccine Program Manager Coordinating GAVI’s Ebola Vaccine Program in collaboration with partners (WHO, Bill & Melinda Gates Foundation, CDC, UNICEF), regulators (FDA) and vaccine manufacturers Key mission: to establish a target product profile tailored to the needs of immune interventions in Global Health, to enable selection of the most suitable Ebola vaccine candidate(s) for use in an Ebola epidemic in collaboration with Manufacturers and Partners and to implement an integrated vaccine work plan in Ebola-affected countriesMid 2013-Mid 2015REGA INSTITUTE, KUL, BelgiumResearch Fellow, Department of Microbiology & ImmunologyMid 2008-Mid 2011BILL & MELINDA GATES FOUNDATION, Seattle, Washington, USASenior Program Officer, Global Health, Vaccine Discovery Initiating and managing grants on vaccine platforms and programs relevant to Global Health (e.g., HIV-1, Malaria, TB, Influenza, Polio...); establishing international product development partnerships on vaccine discovery and immunization programs in Global Health (e.g., with Academia, Biotech Industry, NIH, Welcome Trust, WHO, PATH)Mid 2007 – Mid 2008SOLVAY BIOLOGICALS, Weesp, NLGlobal Project Director Influenza Vaccines Responsible for preclinical development of adjuvanted Influenza vaccines Implementation of commercial-scale production of cell-based methods and expansion of Influenza vaccine production capacity such as to meet DHSS (U.S. Department of Human Health Services) contractual requirements (Pandemic Influenza Preparedness Plan)Mid 2006 – Mid 2007NOVARTIS VACCINES & DIAGNOSTICS, Siena, IT & Emeryville, USADirector, Research Program Leader and Head of AdjuvantsVaccine Research Program/Adjuvant Program responsibilities: Project leader on adjuvanted RSV (Respiratory Syncytial Virus) and Influenza vaccines. Overseeing Preclinical Development of combined seasonal RSV-Influenza vaccine for elderly & high risk adults Shaping the scope and strategy of Adjuvant and Vaccine Delivery Technologies including management of NVD’s adjuvant portfolio, opportunity sourcing, and establishment of an internal interdisciplinary due diligence team for the evaluation of vaccine-relevant extramural opportunitiesMid 1995 – Mid 2006GSK BIOLOGICALS, Rixensart, BEMid 2005 – Mid 2006Associate Director, R&D PartnershipsMajor responsibilities: Outlicensing of analytical and product development activities and providing scientific advice to Vaccine Project Teams on in-licensing opportunities for new vaccine technologies Evaluation of competitive intelligence and intellectual property within the context of R&D collaborations with external partners from the Vaccine Biotech Industry Subcontracting analytical and process activities on GSK Bio vaccine candidatesMid 2001 – Mid 2005Head of Biophysical Vaccine Characterization, Adjuvant Technologies and Alternative Deliveries, R&D New TechnologiesMajor responsibilities: Research Program Leader on Vaccine Formulation Development & Alternative Deliveries and in charge of biophysical characterization activities on adjuvanted vaccine formulations Coordination and follow-up of extramural contracts & collaboration agreements on new immunization strategies and innovative vaccine adjuvant, delivery and formulation technologies Development and validation of vaccine and adjuvant characterization assays Study of adjuvant-antigen interactions and structure-function relationships in vaccine formulations Coordination and resource management of preclinical activities including CMC section of INDs and cGMP production of (adjuvanted) vaccine candidates Planning laboratory activities and establishing outside collaborations with academiaMid 1998 – Mid 2001Senior Project Leader ‘Adolescent Vaccine Projects’Major responsibilities: Project Management on Raw Material Traceability (RAMATRA) and vaccine projects in Late Development, e.g., Herpes Simplex Virus type 2, Hepatitis B, Streptococcus Pneumoniae and Enterotoxic Escherichia Coli (in collaboration with SBL Vaccines, Sweden)Mid 1995 – Mid 1998New Biotech Vaccine Development and QC-QA ManagerMajor responsibilities: Management and coordination of vaccine product development, optimization as well as validation of analytical methods in accordance with regulatory requirements or guidelines and vaccine business constraints Budget management of all activities related to QC assay development and CMC documentation. Transfer from R&D and further development of new QC-relevant characterization techniques on new vaccine candidates (e.g., HSV-2 vaccine, Lyme disease vaccine); contacts with national/ international regulatory and health authorities (e.g., FDA, NIBSC, IHE, WHO,…) on technical dossiers and active participation in pre-IND meetings1990-1994INSTITUTE OF ANIMAL AND ENVIRONMENTAL HYGIENE (Director: Prof. Dr. R. Böhm), UNIVERSITY OF HOHENHEIM/ STUTTGART, GermanySenior Research ScientistMain tasks included: Development of molecular, virological and molecular tools for the detection of viral pathogens in environmental samples of water (e.g., waste water, drinking water and recreational waters), air and soil. Management, coordination, planning and execution of environmental virology research projects including aspects related to the influence of surface active agents on the enhancement of viral infectious behavior Provided appropriate scientific input and advice to public organizations and private companies on microbial sanitation and disinfection methods. In vitro testing of microbicidal activity of disinfectants Tracking and management of research budgets Training and scientific supervision of 4 master degree and 8 doctoral students1987-1990VETERINARY INSTITUTE OF VIROLOGY, IMMUNOLOGY AND MOLECULAR BIOLOGY (Director: Prof. Dr. H. Ludwig), FREE UNIVERSITY OF BERLIN, GermanyResearch Associate Research activities included the setup of molecular, serological and immunological techniques for the diagnosis of viral infectious diseases and/or the characterization of mechanisms underlying natural or vaccine-induced immunity including such that correlate with protection against infectious diseases Research areas primarily included molecular identification, screening and characterization of Equine Herpesviruses and the development and validation of serological tools enabling simple and rapid detection of immune responses against Feline Infectious PeritonitisTeaching Assignments 1998 - 2004 Visiting Professor in Environmental Virology (International Course Programs, ICP; 90 hours of classroom teaching per year) at the European Faculty for Environmental Sanitation (Chair: Prof. Dr. M. Pensaert), University of Ghent, Belgium 1997- 2000 Adjunct Professor (‘Privatdozent’) in Environmental Virology and Zoonotic Diseases at the Faculty of Agricultural Sciences, University of Stuttgart, Germany (40 hours per year of teaching viral and zoonotic diseases to biology students)Supervised PhD theses (as promoter or co-promoter)- Einfluss der Langzeitlagerung von Gülle aud die Tenazität von Viren, 1993; Jürgen Kegele- Untersuchungen zum Vorkommen von luftgetragenen Viren an Arbeitsplätzen in der Müllentsorgung und –verwertung, 1994; Pfirrmann, Andrea- Virologische Untersuchungen zur kombinierten UV-Ozon Behandlung biologisch vorgereinigter Abwässer unter Berücksichtigung des Schwebstoffgehalts, 1994; Stephan KrietemeyerForeign research assignments (minimum 1 month)see under ‘postdoctoral training’ (Postdoctoral Fellowship in Virology at James A. Baker Institute for Animal Health)Organized conferences or symposia BMGF Symposium & Workshop on Dendritic cell – T cell interactions in early HIV infection, December 8-10, 2009, Seattle, USA Organizing Committee 4th International Conference on Vaccines & Vaccination, OMICS group, September 24-26, 2014 Valencia, Spain Organizing Committee Member for EuroVaccines – since 2015 (OMICS Group Conferences)Funds acquired as head or co-promotorInnovation grant of 400k Euro obtained from IWT for period of one year (April 1st 2014- April 1st 2015) on behalf of Univac NV (‘Proof of concept of innovative universal vaccine technology based on activation of natural helper cells by promiscuous pathogen-derived peptides’).OtherCommittee assignments 1998: Assignment as scientific veterinary expert consultant by the Belgian Ministry of Agriculture (’98-’99: Dioxin crisis; 2000-2001: Bovine Spongiform Encephalitis and Footh-and-Mouth Disease) and the Belgian Ministry of Public Health (2002: Provisional legislation and position paper on ‘Nutraceuticals and the Use of Additives and Other Ingredients as Nutritional Supplements in Animal Nutrition’)Professional Affiliations American Society for Microbiology (ASM) American Association for Advancement of Science (AAAS) Infectious Disease Society of America (IDSA) American Association of Veterinary Immunologists (AAVI) Society for Biomaterials HIV Medicine Association Canadian Association for Immunization Research and Evaluation (CAIRE) Society for GlycobiologyNational & International Speaking Invitations (2008-2019) Invited Meeting Chair and plenary presentation: “Biophysics in Adjuvant Formulations”; Immunopotentiators in Modern Vaccines; Montego Bay, Jamaica, 5/21-23/2008 Invited oral presentation: “Adjuvants in Vaccine Formulations”; Infectious Disease Research Institute (IDRI), Seattle, USA, 6/17/2008 Invited keynote presentation: “Adjuvants in Vaccine Formulations: Old Laws, New Paradigms”; CAIRE Master Class, Vancouver, Canada, 9/19/2008 Invited Advisory Panellist and oral presentation: “How to use adjuvants? Keep it simple and safe”; Workshop on Adjuvants and Adjuvanted Preventive and Therapeutic Vaccines for Infectious Disease Indications; Advisory Panel Meeting CBER & NIH, Washington D.C., USA, 12/2-3/2008 Invited keynote presentation: “Understanding Vaccine Adjuvanticity”; CAIRE Master Class, Ontario, Canada, 2/5- 6/2008 Invited keynote presentation: “ Rational Vaccine Design: Where to start?”; Cutting Edge Vaccine for 21st Century, Conference at Flinders University, Adelaide, Australia, 3/12-13/2009 Invited oral presentation: “Bridging the Gap between Adjuvant Discovery and Adjuvant Development”; World Vaccine Congress, Washington D.C., USA, 4/20-24/2009 Invited oral presentation: “Improved Vaccines for Fighting and Controlling Persistent Infections”; Serum Institute of India, Pune, India. 7/23/2009 Invited plenary presentation: “Understanding Vaccine Adjuvanticity: The Biggest Gap & Challenge in Modern Vaccinology”, The 3rd International Conference on Modern Vaccine Adjuvants and Delivery Systems (MVADS), Vienna, Austria, 10/28- 30/2009 Invited oral presentation: “Vaccine strategies to enhance immune responses in neonates”; International Neonatal and Maternal Immunization Symposium (INMIS-2009), Antalya, Turkey; 11/8-9/2009 Invited plenary presentation: “HIV Immune Prevention. From Empiricism to Rational Vaccine Design: “First Dissect, then Direct?”; Workshop on Dendritic Cell - T Cell Interactions in Early HIV Infection, Seattle, USA, 12/8-10/2009 Invited plenary presentation: “ Use New Technologies to Design Vaccines that ‘Help’ Immune Recognition”; World Vaccine Congress Asia, Singapore, 6/8-11/2010 Invited oral presentation: “Rational Vaccine Design and the Search for Correlates of Protection: Which comes first? The Immunotherapeutics & Vaccine Summit, Cambridge, MA, USA, 8/17-19/2010 Invited plenary presentation: “(T-)HELP for Vaccines in Need”; MVAF 2010 , 13-15 October , Cannes, France Invited oral presentation: “Vaccine platforms and Technologies”; 6th Annual GCGH meeting, 2010, 24-27 October, Seattle, USA Invited keynote presentation: “Biophysics in adjuvanted vaccine formulations: The weakest link in modern vaccine development”; Vaccines Europe 2010, 1-2 December, London, UK Invited keynote presentation: “Paradigm shifting concepts in modern vaccine adjuvantation”; MVVA 2010, 17-19 November, Budapest, Hungary Invited opening plenary presentation: “Advancing adjuvant technologies in modern vaccinology: Needs & opportunities”, Immunopotentiators in Modern Vaccines, IV. Int. Conference, 6 – 8 April 2011, Porto, Portugal Invited seminar: “Innovation in Vaccine technologies: Needs and opportunities for novel technologies in modern vaccine development”, National Research Council Canada, 31. May 2011, Ottawa, Canada Invited oral presentation: ”Microneedles with built-in immunoadjuvant properties”, Skin Vaccination Summit, 12-14 October, Washington DC, USA Invited presentation: “Alternative preservatives for vaccines” , WHO Informal Consultation to develop further guidance on vaccines for UNEP-convened Intergovernmental Negotiating Committee Meeting 4 (INC 4), 3-4 April 2012, Geneva, Switzerland Invited oral presentation: “Adjuvant landscaping: Evaluation and rational selection of vaccine adjuvants tailored to the needs of Global Health programs”, organized by Steering Committee on Polio Vaccine Initiative at PATH, 2-3 May 2012, Seattle, USA Invited plenary presentation: “Universally protective vaccines: An achievable/ reasonable objective?”, MVADS (Modern Vaccines Adjuvants & Delivery Systems), Copenhagen Denmark, 4-6 July 2012 Invited oral presentation: “Choosing the 'right' adjuvant: The trickiest part of modern vaccinology”, Informa LifeScience’s 7th annual conference on Veterinary Vaccines, Brussels, Belgium, 5-6 December 2012 Invited plenary presentation: ‘’From empiricism and alchemy to rational vaccine design: A badly needed (r)evolution”, MVAF (Modern Vaccine Adjuvants and Formulations), Lausanne, Switzerland, 15-17 May 2013 Invited presentation: “Innovation in Vaccine Research”, REGA Institute, University Leuven, Belgium, 17 June 2013 Invited plenary presentation: “ Re-thinking Vaccinology”, Immunopotentiators in Modern Vaccines, 7-9 May 2014, Albufeira, Algarve, Portugal Invited presentation: “Nonadjuvanted Universal Vaccines”, Biovision Life Sciences Forum, 5-6 June 2014 Invited presentation: ”Disruptive Innovation in Vaccinology”; 4th International Conference on Vaccines & Vaccination, 24-26 September 2014, Valencia, Spain Invited presentation: “Universally protective synthetic vaccines: The Holy Grail in Modern Vaccinology”, 2nd International Conference on Systems & Synthetic Biology, August 18-20, 2016, London, UK Invited presentation: “Universally protective vaccines: A revolution in modern vaccinology”, International Precision Vaccines Conference, October 23-24, 2017, Boston, MA USA Invited presentation: “Universally protective vaccines: A revolution in modern vaccinology”, 21st World Congress and exhibition on Vaccines, Vaccination & Immunization, November 09-10, 2017, Vienna, Austria Keynote presentation: “Translational Vaccinology: A myth?”, 21st World Congress and Exhibition on Vaccines, Vaccination & Immunization, November 09-10, 2017, Vienna, Austria and Modern Vaccines Adjuvants Formulation, May 02-04, 2018, Leiden, The Netherlands Keynote presentation: “Why don’t our vaccines reach the high-hanging fruit?” Euro Vaccines 2019, 6th Euro Global Summit and Expo on Vaccines & Vaccination, June 03 -04, 2019, London, UK., Keynote presentation: “Quo vadis vaccinology? An urgent call for change!”, 2nd European Congress on Vaccine R&D and Vaccination, EuroSciCon, June 11-12, 2019, Prague, Czech Republic Invited presentation: “Why current vaccine approaches fail in reaching the high-hanging fruit?“, Vaccines Research and Development, November 18-20, 2019, Boston, USA Keynote presentation: “Why should current Covid-19 vaccines not be used for mass vaccination during a pandemic?” Vaccines Summit Ohio (VSOHI021), March 1-3, 2021, Ohio, USAScientific and Advisory Panels Modern Vaccine Adjuvants and Delivery Systems (MVADS) 2006; 12-14 Sept, The Royal Society of Medicine, London, UK Immunopotentiators in Modern Vaccines (IMV) 2008; 21-23 May 2008, Montego Bay, Jamaica Workshop on Adjuvants and Adjuvanted Preventive and Therapeutic Vaccines for Infectious Disease Indications; Advisory Panel Meeting CBER & NIH, 2-3 December 2008, Washington D.C., USA Modern Vaccine Adjuvants and Delivery Systems (MVADS) 2009; 28-30 Oct 2009, The Austrian Industrial Association, Vienna, Austria Scientific Working Group on Immunogens and Antigen Processing. Global HIV Vaccine Enterprise; 15-16 July 2009, New York, USA Modern Vaccine Adjuvants and Formulations (MVAF) 2010 , 13-15 October , Cannes, France Joint annual adjuvant development and discovery contractors meeting (NIAID, NIH); 18-20 October 2010, Bethesda, USA Modern Veterinary Vaccines ad Adjuvants, (MVVA) 2010, 17-19 November, Budapest, Hungary Immunopotentiators in Modern Vaccines (IMV), IV. Int. Conference, 6 – 8 April 2011, Porto, Portugal 2010-2012: Chairing multiple vaccine sessions at World Vaccine Congress and European Vaccine Congress WHO Informal Consultation and Advisory meeting to develop further guidance on vaccines for UNEP-convened Intergovernmental Negotiating Committee Meeting 4 (INC 4), 3-4 April 2012, Geneva, Switzerland MVADS 2012, 4-6 July, Copenhagen Denmark MVAF (Modern Vaccine Adjuvants and Formulations), Lausanne, Switzerland, 15-17 May 2013 Immunopotentiators in Modern Vaccines, 7-9 May 2014, Albufeira, Algarve, Portugal Organizing Committee 4th International Conference on Vaccines & Vaccination, OMICS group, September 24-26, 2014 Valencia, Spain Organizing Committee Member for EuroVaccines – since 2015 (OMICS Group Conferences) MVAF (Modern Vaccine Adjuvants and Formulations), Leiden, The Netherlands, 02-04 May 2018 Organizing Committee Member for Vaccine R&D and Vaccination, EuroSciCon, June 11-12, 2019, Prague, Czech RepublicPosters and invited lectures (1988-1997)Posters Vanden Bossche, G., Krietemeyer, S.: Application of anionic detergents for improvement of the isolation rate of enteroviruses from waste water; 6th International Symposium on Microbial Ecology, Barcelona, Spain, 6-11 .09.1992 Vanden Bossche, G.: The impact of interfacial interactions on the in vitro infectivity of detergent-treated virus samples; 2nd International Conference on the Fundamental Aspects of Bioadhesion and Flocculation and their Implications in Technological, Ecological and Medical Fields, Bioadhesion II, University of Louvain-la-Neuve, Belgium, 23- 27.05.1993 Vanden Bossche, G.: In vitro modulation of virus infectivity by surface- active agents; 9th International Congress of Virology, Glasgow, Scotland, 8-13.08.1993 Krietemeyer, S., Vanden Bossche. G., Schmitt, J., Flemming, H.C.: Einsatz von ionischen Tensiden zum Virus- nachweis in Biofilmen aus Trinkwasseraufbereitungssystemen (Use of ionic surfactants for the detection of viruses in biofilms from drinking water treatment systems); Bio-Engineering Congress VAAM-DGHM, Hannover, F.R.G., 7-9.03.1994 Vanden Bossche, G., Krietemeyer, S.: Use of ionic detergents for the detection of human enteroviruses in biofilm samples from drinking water systems; International Workshop on New Approaches in Microbial Ecology, Elsinore, Denmark, 21-25.08.1994 Vanden Bossche, G., Krietemeyer, S.: Isolierung von humanen Enteroviren aus Biofilmen von Trinkwasser- aufbereitungssystemen mittels Detergens-Konditionierung ( Isolation of human enteroviruses in biofilms of drinking water treatment systems using detergent-conditioning); 46th Congress of the German Association for Hygiene and Microbiology (DGHM), Kiel, F.R.G., 26-29.09.1994Lectures 'Neuere Entwicklungen (auch am lebenden Tier) in der Coronavirus-Diagnostik' Berliner Tierärztliche Gesellschaft, Berlin, F.R.G., 15.06.1988 (New developments (also in live animals) of Coronavirus diagnostics) 'Viral diseases in cats: A survey' Deutscher Edelkatzen-Verein, International Congress Centrum, Berlin, F.R.G., 16.11. 1988 ‘Zur Standardisierung and Interpretation der serologischen Coronavirus-Diagnostik bei der Katze: Korrelation zum klinischen bzw. anatomisch-pathologischen Befund' (Coronavirus diagnostics in cats: Standardization and interpretation of serological results: Clinical and anatomo- pathologic correlates) Bundesverband pralctischer Tierarzte, Hamburg, F.R.G., 7.06.1988 ‘Molecular epidemiology of Equine Herpesvirus type 1 (EHV-1) in non-equine hosts' 9th Intern. Symp. of Infections of the reproductive system of some domestic animal species, Perugia, Sept. 1988 'Rol van surfactant in de pathophysiologie van chronische bronchitis bij het paard' (The role of surfactant in the pathophysiology of chronic bronchitis in horses) Vereniging van Belgische Paardenpractici, Brussels, Belgium, 10.12.1988 ‘Zur Anwendung von Zell-Elisa, Immunblotting and Genom-Hybridisierung im virologischen Labo’ (The use of Cell-Elisa, Immunoblotting and genome hybridization in virological labs) Deutscher Verband Technischer Assistenten in der Medizin e. V., 5th 'Deutscher MTA- Kongress', Mannheim, F.R.G., 8-10.03.1989 'Die Parvovirus-Typ 2-Infektion beim Hund: Diagnostik and Immunprophylaxe' (Diagnostics and immune prophylaxis of Parvovirus-Typ 2-Infections in dogs) Berliner Tierärztliche Gesellschaft, Berlin, F.R.G., 10.05.1989 ‘ Zur Wahl der Testviren bei der Prüfung chemischer Desinfektionsmittel in der Veterinärmedizin’ (The choice of test viruses in testing of chemical disinfectants in veterinary medicine) Deutsche Veterinarmedizinische Gesellschaft, 3th Hohenheimer Seminar, Stuttgart, F.R.G., 18-19.11.1990 'Fortschritte bei der Diagnose and Prophylaxe virusbedingter Infektionen’ (Progress in the diagnosis and prophylaxis of viral infections) Sanitätsamt der Bundeswehr für medizinischen ABC-Schutz, Munich, F.R.G., 20.11.1990 'Zur Pathogenese and Epidemiologie der felinen infektiösen Peritonitis (FIP)' (Pathogenesis and epidemiology of Feline Infectious Peritonitis (FIP)) Stuttgarter Tierärztliche Gesellschaft, Stuttgart, F.R.G., 4.12.1990 ‘Einsatz von Carbonsäuren zur Dekontamination von Futtermitteln and Küchenabfällen' BASF-Aktiengesellschaft, Ludwigshafen, F.R.G., 11.09.1991 'Fehlinterpretation der viruziden Wirksamkeit bei der Prüfung tensidhaltiger Desinfektionsmittel' Osterreichische Gesellschaft für Hygiene, Mikrobiologie and Präventivmedizin. 12. Dosch-symposium, Vienna, Austria, 2-3.11. 1992 ‘Alternative Desinfektionsmittel - Die Desinfektionswirkung von Kalkanstrichen and organischen Säuren' Workshop 'Desinfektion bei der Tierseuchenbekampfung', Allmendingen, F.R.G., 16.06.1992 'Optimization of virus recovery from sewage by crossflow filtration' 6th International Symposium on Microbial Ecology, Barcelona, Spain, 6-11.09.1992 ‘Neue Methoden zur Potenzierung der Nachweisrate von infektiösen Viruspartikeln in Umweltproben' (New methods for the enhanced detection of infectious viral particles in environmental samples) Institute of Virology, Molecular Biology and Immunology, Free University of Berlin, Berlin, F.R.G., 8.02.1993 'Neue Methoden zur Potenzierung der Nachweisrate von infektiösen Viruspartikeln in Umweltmedien' Umweltbundesamt, Symposium 'Uberwachungsmethoden Gentechnik: Nachweisverfahren für Mikroorganismen, Viren and Gene in der Umwelt', TU Berlin, Berlin, F.R.G., 25-26.03.1993 'Vorkommen, Isolierung und Desinfektion epidemiologisch relevanter Viren in Abwasser' (Occurrence, Isolation and Disinfection of epidemiologically relevant viruses in waste water) Stuttgarter Tierärztliche Gesellschaft, Stuttgart, 12.05.1993 and Aulendorf, 13.05.'93, F.R.G. ‘Evaluation of virucidal activity of detergent-containing disinfectants' Unilever Research Colworth Laboratory, Sharnbrook, Bedford, England, 29.07.1993 'Die Prüfung chemischer Desinfektionsmittel auf viruzide Wirksamkeit: Hinweise auf grundsätzliche methodische Unzulänglichkeiten'(The testing of chemical disinfectants for virucidal efficacy: Evidence of fundamental methodological shortcomings')45th Congress of the 'Deutsche Gesellschaft für Hygiene and Mikrobiologie - DGHM', Karlsruhe, F.R.G., 27- 30.09.1993 'Einfluf von Grenzflächenphänomenen auf das infektiöse Verhalten unbehüllter Viren: Fakten and Konsequenzen für Forschung and Praxis'(Impact of surface active phenomena on the infectious viral behavior of uncoated viruses: Facts and consequences for research and practice) Workshop "Kolloidchemische Aspekte der Virusinfektiosität", University of Hohenheim, Stuttgart, F.R.G., 10.03.1994 'Wechselwirkz{ngen zwischen Viren and oberflächenaktiven Verbindungen in Abwasser: Implikationen für die Hygiene von Gewässern'(Interactions between viruses and surface active compounds in waste water: Implications for water hygiene practice)State Institute for Environmental Hygiene of Water, Soil and Air (Wa-Bo-Lu), Federal Public Health Authority (BGA), Berlin, F.R.G., 13.04.1994 'Kolloidchemische Einflüsse auf das Infektiositätsverhalten von (unbehüllten) Viren'(Colloidal-chemical influences on the infectious behavior of non-enveloped viruses)Federal Research Centre for Virus Diseases of Animals (BfA für Viruskrankheiten), Tübingen, F.R.G., 21.04.1994 'Humanpathogene Viren and ihr Verhalten bei der Wassergewinnung and Aufbereitung'(Human pathogenic viruses and their behavior in terms of water production and treatment)5th International Symposium "Contamination of the Environment by Viruses and Methods of Control", University of Agriculture, Forestry and Renewable Resources, Vienna, Austria, 3-4.05.1994 'Detergent conditioning of environmental samples: A (The?) most sensitive method for the detection of viral infectivity?'International Symposium on Health-Related Water Microbiology, Budapest, Hungary, 24-30.07.1994 ‘Epidemiological importance of viruses pathogenic to man and spreading in soil and ground water'International Conference on Waterborne Infectious Diseases, Haifa, Israel, 02-06.09.1994 'Emission von Viren (an verschiedenen Arbeitsplätzen) in Kompostwerken and anderen Müllverarbeitenden Betrieben'(Emission of viruses (at several different locations) in composting and other waste processing facilities)5th Hohenheimer Seminar Nachweis and Bewertung von Keimemissionen bei der Entsorgung von kommunalen Abfällen sowie spezielle Hygieneprobleme der Bioabfallkompostierung', University of Hohenheim, Stuttgart, F.R.G., 5-6.10.1994 Neue Strategien zur Immunprophylaxe von Virusinfektionen und Beispiele für deren Anwendung in der Veterinärmedizin ' (New strategies for immunoprophylaxis of viral infections and examples of their application in veterinary medicine)University of Hohenheim, Stuttgart, Germany, 05.12.1996 `Zum Einsatz von rekombinanten Virusvektoren in der Veterinärmedizin zur Therapie and Immunprophylaxe ' (The use of recombinant viral vectors in veterinary medicine for therapy and immunoprophylaxis)University of Hohenheim, Stuttgart, Germany, 10.01.1997Publications G. Vanden Bossche (1987-1995 ; 2017)
- A1 PUBLICATIONS
- 1. Vanden Bossche, G. (1994): Alterations of viral infectious behavior by surface active agents; Microbiol. Research 149 (2), 105-114 Vanden Bossche, Geert
- 2. Vanden Bossche, G. (1994): Use of ionic detergents for enterovirus recovery from waste water; Microbiol. Research 149 (3), 231-240
- 3. Vanden Bossche, G., Wustmann U., Krietemeyer, S. (1994): Ozone disinfection dynamics of enteric viruses provide evidence that infectious titer reduction is triggered by alterations to viral colloidal properties; Microbiol. Research 149(4), 351-370
- 4. Vanden Bossche, G. (1995): The impact of interfacial interactions on poliovirus infectivity in detergent-treated mono- layer cultures; Microbiol. Research 150 (3), 247-263
- 5. Pfirrmann, A., Vanden Bossche, G. (1994): Vorkommen und Isolierung von humanen Enteroviren aus der Luft von Abfallbeseitigungs- und –verwertungsanlagen; Zbl. Hyg. Umweltmed. 195, 136-144 (Occurrence and isolation of airborne human enteroviruses from the air from waste-disposal and utilization plants)
- ARTICLES NOT BELONGING TO THE A1 CATEGORY
- 1.Vanden Bossche, G. (1987): Chronische Otitis media-interna mit Beinträchtigung des Nervus facialis und Nervus vestibulocochlearis: Fallbericht und allgemeine Betrachtungen; Pferdeheilkunde 3, 157-164 (Chronic otitis media-interna and impact on the facial and vestibulocochlear nerve: Case report and general considerations)
- 2. Wintzer, H.-J., Vanden Bossche, G., Ludwig, H., Bischof, B. (1987): Seuchenverlauf nach EHV-1-Infektion in einem Reitpferdebestand; Dtsch. Tierärztl. Wschr. 94, 149-152 (Epidemiology of EHV-1 infection in a horse riding stable)
- 3. Ludwig, H., Chowdhury, S.I., Vanden Bossche, G., Wintzer, H.-J., Krauser, K. (1987): Neurologische Symptomatik bei einer Warmblutstute mit akutem tödlichem Verlauf. Molekuläre Charakterisierung des Gehirnisolates und patho- logische Korrelate; Berl. Münch. Tierärztl. Wschr. 100, 147-15 (Neurological symptoms in a warmblood mare with acute and fatal clinical outcome. Molecular characterization of brain tissue samples and pathological correlates)
- 4. Vanden Bossche, G. (1987): Hämatologische und biochemische Befunde beim gesunden Esel; Pferdeheilkunde 5, 277-280 (Hematology and biochemical findings in healthy donkeys)
- 5. Vanden Bossche, G., Krauser, K. (1988): Kachexiesyndrom bei einer Eselstute infolge einer toxisch-infektiösen Enteritis. 1ste Mitteilung: Primärsymptomatologie und Pathologie (5a); 2te Mitteilung: Anämie als sekundärer Symptomenkomplex (5b); 3te Mitteilung: Hyperlipämie als sekundäre Komplikation (5c); Berl. Münch. Tierärztl. Wschr. 101, 113-116 (5a), 116-119 (5b), 190-193 (5c) (Cachexia syndrome in a donkey mare caused by toxic-infectious enteritis. 1. Primary symptoms and pathology; 2. Anaemia as secondary symptom complex; 3. Hyperlipaemia as secondary complication)
- 6. Vanden Bossche, G., Ludwig, H. (1989): Zur klinischen Bedeutung der serologischen Coronavirus-Diagnostik bei der Katze; REPORT: Physiologie, Diagnostik und Therapie in der Kleintiermedizin 28, 15-19 (EFFEM-Forschung für Heim- tiernahrung) (The clinical relevance of serology to Coronavirus diagnostics in cats)
- 7. Vanden Bossche, G. (1990a): Zur Anwendung, zum Prinzip und zur praktischen Durchführung der SDS-PAGE und Western Blotting. Teil I: Theoretische Grundlagen; Fachzeitschrift MTA Januar, 11-14 (Overall principle, application and practical implementation of SDS-PAGE and Western Blotting. Part I: Theoretical background)
- 8. Vanden Bossche, G. (1990b): Zur Anwendung, zum Prinzip und zur praktischen Durchführung der SDS-PAGE und Western Blotting. Teil I: Praktische Dürchführung; Fachzeitschrift MTA Februar, 110-115 (Overall principle, application and practical implementation of SDS-PAGE and Western Blotting. Part II: Practical implementation) Vanden Bossche, Geert
- 9. Vanden Bossche, G. (1990a): Zur epizootiologischen Interpretation der Coronavirus-Serologie bei gesunden und non-FIP (Feline Infektiöse Peritonitis) kranken Katzen mittels der indirekten Immunfluoreszenz (IF); Kleintierpraxis 35, 189-191 (Epizootiological considerations on the interpretation of serologic results from Coronavirus diagnostics in healthy and non-FIP (Feline Infectious Peritonitis) diseased cats using an indirect immunofluorescence technique)
- 10. Vanden Bossche, G. (1990b): Zur Serodiagnose der Felinen Infektiösen Peritonitis (FIP) mittels einem indirekten Immunfluoreszenz-Test (IFT): Eine statistische Bewertung der diagnostischen Treffsicherheit; Kleintierpraxis 35, 201-213 (Using an indirect immunofluorescence technique for serodiagnosis of Feline Infectious Peritonitis (FIP):A statistical evaluation of diagnostic accuracy)
- 11. Dörwald, M.-L., Vanden Bossche, G., Gerull, A. (1991): Zur Surfactant-Phospholipidzusammensetzung im Tracheo- bronchialsekret des Pferdes und ihrer klinischen Relevanz für die Beurteilung des Lungenstatus bei chronisch lungen- kranken Pferden; Wiener Tierärztliche Monatsschrift 78, 118-126 (The composition of surfactant phospholipid in tracheobronchial secretions from horses and clinical relevance thereof for the assessment of pulmonary function in horses with chronic lung disease)
- 12. Vanden Bossche, G., Dörwald, M.-L., Gerull, A. (1991): Belastungsinduzierte Veränderungen der Surfactantphospho- lipidzusammensetzung im Tracheobronchialsekret von gesunden und chronisch lungenkranken Pferden; Wiener Tier- ärztliche Monatsschrift 78, 145-152 (Stress-induced changes of surfactant phospholipid composition in tracheobronchial secretions of healthy horses and horses with chronic lung disease)
- 13. Vanden Bossche, G., Strauch, D. (1991): Zur Wirksamkeit von Flächendesinfektionsmitteln und ihrem Einsatz in der Tierhaltung; BL-Journal-Laborpraxis in Biologie und Landwirtschaft April/Mai, 110-126 Review on the effectiveness of surface disinfectants and their use in animal husbandry)
- 14. Vanden Bossche, G. (1991): Zum Einsatz von Säuren als Desinfektionsmittel: Spezifische Wirkungsmechanismen und – spektren sowie typische Anwendungseigenschaften. Hygiene + Medizin April, 167-172 (Review on the use of acids as disinfectants: Specific mechanisms of action, spectrum of effects as well as specific applications)
- 15. Philipp, W., Rapp, A., Kegele, J., Vanden Bossche, G., Strauch, D. (1992): Einfluss der Langzeitlagerung von Gülle auf die Tenazität von Krankheitserregern; Tierärztl. Umschau 47, 521-524 (Influence of long-term storage of manure on the tenacity of pathogens)
- 16. Vanden Bossche, G. (1993): The impact of physicochemical interactions on viral infectivity in water samples. Proceedings of 4th International Symposium on Contamination of the Environment by Viruses and Methods of Control, Vienna; September 3-4, 1993. In: Wiener Mitteilungen, 34-42
- 17. Vanden Bossche, G., Krietemeyer, S. (1994): Detergent conditioning: A (The) most sensitive method for the detection of enterovirus infectivity in biofilm samples; Wat. Sci. Tech. 30, 2231-2239
- 18. Vanden Bossche, G. (1995): Colloidal aspects of enteroviral infectivity in aqueous environments (with special emphasis on Poliovirus type 1). Habilitation Thesis, http://lib.ugent.be/nl/catalog/rug01:000349688
- 19. Vanden Bossche (2017): Re-thinking vaccinology: “Act universally, think NK cells ?”; J Molec Immunol Res. 1(1), 1-6
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EVIDENCE TIMELINE
1988
https://pubmed.ncbi.nlm.nih.gov/3401205/
Case Reports
Berl Munch Tierarztl Wochenschr
. 1988 Jun 1;101(6):190-3.
[Cachexia syndrome in a donkey mare due to a toxic infectious enteritis. 3. Hyperlipemia as a secondary complication]
[Article in German]
PMID: 3401205
No abstract available
1994
https://pubmed.ncbi.nlm.nih.gov/7921892/
Microbiol Res
. 1994 Jun;149(2):105-14. doi: 10.1016/s0944-5013(11)80104-7.
Alteration of viral infectious behavior by surface active agents
Affiliations expand
PMID: 7921892
Abstract
Phosphate buffered saline (PBS) and wastewater retentate, which had been adjusted to the same level of pH and ionic strength by addition of a concentrated PBS solution, were experimentally seeded with polio- or parvovirus and treated with various concentrations of sodium dodecylsulfate (SDS) and dodecyltrimethylammoniumbromid (DTAB), respectively. Upon subsequent assessment for viral infectivity of the samples in Buffalo green monkey kidney cell cultures, infectivity modulating effects of DTAB in PBS and of SDS in retentate appeared to be largely affected by the electrical charge of the suspended virions. However, if PBS or retentate samples were treated with SDS or DTAB respectively, different isoelectric properties between polio- and parvovirus particles were less likely to affect the detergent concentration required for optimal virus recovery. Moreover, in the presence of soluble organics, optimal virus recovery rates were obtained with much lower detergent concentrations if the samples had been treated with DTAB instead of SDS. Measurement of the effective critical micelle concentration as well as multiangle electrophoretic light scattering (MELS) seemed to provide a simple approach to monitoring colloidal stability of multicomponent viral particle (VP) suspensions upon the addition of ionic detergents. By measuring zeta potential distribution, MELS offers additional information about alterations to electrical viral surface properties. Since the behavior of VPs is well known to largely depend upon their electrical characteristics within the environment in which they exist, there is substantial evidence that MELS can provide valuable guidelines in studying optimal detergent-treatment conditions for virus recovery from aqueous suspensions.
1994
https://pubmed.ncbi.nlm.nih.gov/7802896/
Comparative Study
Zentralbl Hyg Umweltmed
. 1994 Aug;196(1):38-51.
[Occurrence and isolation of human enteroviruses from the air of waste removal and disposal plants]
[Article in German]
A Pfirrmann 1, G vanden Bossche
Affiliations expand
PMID: 7802896
Abstract
Aerosols from waste treatment plants were examined with regard to the presence of airborne viruses. For the purpose of a comparative evaluation, two different collecting devices consisting of an electroprecipitator and a special-impinger apparatus were used for extraction and collection of viruses from air samples. The collected suspensions were concentrated and fractionated by means of hydroextraction in combination with a differential centrifugation procedure. After solubilisation of the sedimented material with the anionic detergent, sodium-dodecylsulfate, and following ultrasonic treatment, viral infectivity could be demonstrated in 12 out of 36 examined specimens, after inoculation on BGM cells. The highest virus isolation rates were obtained with the electroprecipitator. Based on the results of investigations of biological, physicochemical as well as antigenic characteristics, the isolated strains revealed to belong to the family of Picornaviridae. According to the results of additional characterization assays, the isolates were identified as Coxsackie-B and ECHO-viruses. The linkage between the occurrence of these viruses and a possible risk of infection for humans remains to be elucidated by further epidemiological studies. However, the results of the present work indicate that, besides of an increased dust and germ concentration in such facilities, there is substantial evidence of increased viral contamination as well. Enteroviruses are generally considered as indicator viruses revealing the presence of viral contaminants in tap water and sewage. As human enteroviruses can be regularly isolated from such aerosols, the detection of these viruses in air samples may also be an appropriate criterion to estimate the amount to which virus concentrations may build up within waste treatment plants.
1994
https://pubmed.ncbi.nlm.nih.gov/7842234/
Microbiol Res
. 1994 Nov;149(4):351-70. doi: 10.1016/S0944-5013(11)80083-2.
Ozone disinfection dynamics of enteric viruses provide evidence that infectious titer reduction is triggered by alterations to viral colloidal properties
G Vanden Bossche 1, U Wustmann, S Krietemeyer
Affiliations expand
PMID: 7842234
Abstract
The inactivation dynamics of three enteric virus species (polio-, rota- and parvovirus) were analysed in different aqueous suspensions by using O3 under continuous flow conditions. A mathematical model for the reaction rate of infectious titer reduction was proposed, based on the thermodynamic principles of phase behaviour of colloids suspended in aqueous environments. Up to a certain threshold dosage of residual ozone (RO), and depending on the type of test virus and the ionic or organic load in the stock suspension, the logarithm of the reaction rate constant of viral inactivation rate was observed to vary in a rather sigmoidal manner with log RO concentration. Data from photon correlation spectroscopy, electron microscopy and tensiometric analysis suggested that below the threshold RO, the pattern of virus inactivation dynamics reflects the varying potential of different-sized viral particles (VPs) to adsorb to the cellular monolayer. There is strong evidence that oxidant-induced surface activity of organic matter causes redistribution of VP infectivity. This hypothesis was statistically corroborated inasmuch as experimental inactivation data proved to be satisfactorily fitted by a logistic equation. It was concluded that viral infection, and thus viral inactivation, is a complex process which is governed largely by the classical laws of colloidal behaviour. The latter is suggested to appreciably determine the capability of inoculated VPs to infect host cultures. This notion may especially be cause for concern when regulatory requirements for virus disinfection are being based on titration results from in vitro testing procedures.
1995 - Microbiol Res : "The impact of interfacial interactions on poliovirus infectivity in detergent-treated cell monolayer cultures"
https://pubmed.ncbi.nlm.nih.gov/7551734/
Microbiol Res
. 1995 Sep;150(3):247-63. doi: 10.1016/s0944-5013(11)80004-2.
G Vanden Bossche 1 (Institut für Umwelt- und Tierhygiene sowie Tiermedizin-460, Universität Hohenheim, Stuttgart, Germany.)
PMID: 7551734
Abstract
Monolayer cultures of Buffalo green monkey (BGM) kidney cells were inoculated with different aqueous solutions of anionic detergents prior to infection with polio-myelitisvirus type 1 (PMV-1). Alteration of inoculated cell culture monolayers was assessed by polarized light microscopy. Based on their visual appearance, altered monolayers were arbitrarily assigned different rating categories (r.c.) ranging from 1 to 8. For each detergent concentration, the rate of monolayer destruction was recorded and graphically integrated into the plots of r.c. against detergent concentration. In addition to a direct detergent-mediated alteration of the cellular monolayers, inoculation of detergent-conditioned BGM cultures with PMV-1 apparently affected virus-mediated alteration as well. The type of alteration as well as the initial rate of cytopathic destruction of the monolayer depended on several factors including the stereochemical properties of the detergent used, the final detergent concentration as well as the organic content and inoculation volume of the preconditioning solution, and the infectious titer of the viral inoculum. Moreover, infectivity kinetics revealed that cytopathic effects may be reactivated after a period of viral inhibition. In this way, at least two cycles of virus generation successively alternating with cell proliferation could be recorded simply by supplementing the system with energy for growth. From the presented results, it became apparent that modifications of cell surface activity contribute to virus infectivity mechanisms. Since treatment of aqueous PMV-1 suspensions has been previously described to largely affect viral infectious titers, viral uptake seems to be triggered by the phase behavior of viral particles upon contact with the plasma membrane. Therefore, aquatic samples that have been treated with anionic detergents in order to optimize virus isolation rates should be extensively washed prior to inoculation on cell culture.
2015 (August)
https://www.longdom.org/conference-abstracts-files/2157-7560.S1.027_017.pdf
2015-08-omics-6th-international-euro-global-summit-and-expo-on-vaccines-and-vaccination.pdf
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Effective vaccine design: Back to the drawing board?
Geert Vanden Bossche
REGA Institute, University Leuven, Belgium
To eliminate safety risks related to infectivity, inactivated pathogens and, more suitably, well-characterized pathogen-derived antigens (Ags) have increasingly been used as immunogens in ‘modern’ vaccines. The selection of these Ags is usually based on their capacity to naturally induce immune responses that ‘correlate’ with protection. These Ags, however, are often variable (e.g., conformational Bc epitopes) and/ or subject to immunogenetic restriction (e.g., linear, cell-bound epitopes). In addition, the immunogenicity of ‘good’ vaccinal Ags is largely dependent on memory CD4+ T helper cells. However, activation of the latter upon natural infection or foreign Ag exposure of genetically predisposed subjects has been associated with immune pathology. Priming of CD4+ T helper cells by adjuvant vaccines is, therefore, increasingly raising safety concerns. On the other hand, Ags that are highly conserved, universal and of vital importance to the pathogen (hence, called ‘protective’) are either not included in contemporary vaccines or not effectively recognized by the host immune system since capable of imitating self- molecules and outcompeted by other pathogen-derived ‘decoy’ epitopes for binding to MHC molecules. Hence, we consider that new technologies enabling immune targeting of such protective epitopes by natural, universal (i.e., nonallotype-specific) immune helper cells is the new Holy Grail for modern vaccinology.
Biography
Geert Vanden Bossche obtained his DVM at the Veterinary Faculty of Ghent and his PhD in Virology at the University of Hohenheim, Stuttgart. Following his Postdoctoral training in virology, immunology and molecular biology at the Free University of Berlin and Hohenheim (Germany), where he subsequently held adjunct faculty appointments, he transitioned to the Vaccine Industry where he served various senior roles in both early and late vaccine development at GlaxoSmithKline Biologicals, Novartis Vaccines & Diagnostics and Solvay Biologicals. He then joined the Bill & Melinda Gates Foundation to serve as SPO in Vaccine Discovery for Global Health. He is founder of UNIVAC LLC in the US and UNIVAC NV in Belgium and visiting scientist at the REGA Institute, University of Leuven (Belgium). He is board certified in virology and microbiology, the author of over 30 publications, and inventor on several patent applications. He has presented vaccine- and adjuvant-related topics at multiple international congresses.
2015 ( November 02-04 in Baltimore, USA ) - United Scientific Group "Vaccines R&D 2015 Symposium - A NEW ERA IN VACCINE DISCOVERY"
Keynote speakers include : Dr. Robert Wallace Malone (born 1959)
2015 Program : [HI004E][GDrive] / Conference Book PDF : [HI004H][GDrive]
United Scientific Group Committee for the 2015 Vaccines R&D Symposium ( Dr. Geert Vanden Bossche on the committee )
Jay A Berzofsky, M.D., Ph.DChief, Vaccine Branch, Center for Cancer Research, National Cancer Institute, NIH, USADr. Jay A Berzofsky was appointed chief of the new Vaccine Branch, Center for Cancer Research, National Cancer Institute, in 2003 after having served as chief of the Molecular Immunogenetics and Vaccine Research Section, Metabolism Branch, National Cancer Institute, NIH, since 1987. He graduated Summa cum Laude from Harvard (1967), and received a Ph.D. and M.D. from Albert Einstein College of Medicine. After interning at Massachusetts General Hospital, he joined NIH in 1974. Dr. Berzofsky's research has focused on antigen processing and presentation by MHC molecules, the structure of antigenic determinants, cytokine and regulatory cell control of T cell function and avidity, and translation to the design of vaccines for AIDS, malaria, cancer, and viruses causing cancer. He has published 476 scientific works. Dr. Berzofsky has received a number of awards, including the U.S. Public Health Service Superior Service Award, the 31st Michael Heidelberger Award, the McLaughlin Visiting Professorship, the Australasian Society for Immunology Visiting Lectureship, and the Tadeusz J. Wiktor Memorial Lectureship. He is the past president of the American Society for Clinical Investigation, and a fellow of the American Association for the Advancement of Science and was elected Distinguished Alumnus of the Year for 2007 by the Albert Einstein College of Medicine. He was also elected chair of the Medical Sciences Section of the American Association for the Advancement of Science (AAAS) 2007-08. He won the NIH Director's Award and NCI Merit Award in 2008 and a Merit Award in 2011.
Magdalena Tary Lehmann M.D., Ph.DChief Scientific Officer, Cellular Technology Limited (CTL), USADr. Magdalena Tary Lehmann received her M.D. and Ph.D. in Immunology, both from the University of Tubingen, Germany. Her postdoctoral training in Immunology was at the University of California, Los Angeles. Thereafter, she went on to Case Western Reserve University as a faculty member, where she was awarded tenure and appointed Associate Professor in the Department of Pathology in 2003. As Chief Scientific Officer for CTL, she provides guidance and oversight for technical operations, ensuring the ongoing scientific excellence of the company. For more than 10 years, she has worked with various pharmaceutical and biotechnology clients in developing, validating and performing regulated immunology assays in CTL's GLP- and CLIA- compliant laboratory.
Michael G Hanna Ph.DVaccinogen Inc., USADr. Michael G Hanna, Jr. received his Ph.D in experimental pathology and immunology from the University of Tennessee (TN, USA) in the 1960s. He was a consultant with NASA for the lunar receiving laboratory during Apollo 11 and 12, for which his expertise in immunology was used in the testing of the lunar core powder for immunogenic or pathogenic materials. Dr. Hanna served during 1974–83 as Director of the National Cancer Institute, Frederick Cancer Research Center (MD, USA). He was Chief Operating Officer during 1985–94 of Organon Teknika/Biotechnology Research Institute and Senior Vice President of Organon Teknika Corporation, a subsidiary of Akzo Nobel, Netherlands. He developed and obtained approvals for TICE BCG for the treatment of carcinoma in situ (CIS) bladder cancer, which remains the standard of care for prophylaxis of recurrence of superficial bladder cancer and therapy of CIS. Subsequently, Dr. Hanna founded PerImmune Inc., for which he served as President and Chief Executive Officer before it merged with Intracel Corp. in 1998. He continued to work for Intracel Resources as Chief Scientific Officer and Chairman. In 2007, Dr. Hanna founded Vaccinogen Inc., where he served as Chairman and CEO. Currently, Dr. Hanna is Chairman Emeritus. The company is a pioneer in the field of cancer vaccines and is developing OncoVAX, an autologous vaccine designed to elicit a specific immune response against cancer cells. The Phase 3 vaccine is being investigated for treatment mainly of colon cancer, but also for melanoma and renal cell carcinoma. In addition to cancer therapy research and development, Dr. Hanna has been involved in Homeland Security. He served as Chairman of the Department of Commerce Biotechnology Advisory Committee (1984–9) and also participated in the Department of Defense Technical Working Group for Biotechnology (1988–9). PerImmune completed a Department of Defense contract to manufacture the current effective therapeutic for Botulinum toxin, an equine heptavalent anti-toxin. Dr Hanna's research resulted in over 225 publications in international peer-reviewed journals and book chapters, and he holds 10 patents related to immunotherapy. Dr Hanna has been the recipient of numerous honors and awards and has served on many editorial boards, including for Human Vaccines & Immunotherapeutics.
Michael Hust, Ph.DTechnische Universität Braunschweig, GermanyProf. Dr. Michael Hust studied biology at the Carl von Ossietzky Universität in Oldenburg, Germany, from 1993-1999. He received his PhD from the Leibniz Universität in Hannover, Germany, in 2002. Since end of 2002 he is working as group leader at the Technische Universität Braunschweig, Germany. In 2011, he finished his professorial dissertation (Habilitation, venia legendi for Biotechnology) and was appointed as Privatdozent (PD). In 2014 he was appointed as extraordinary professor (außerplanmäßige Professur) for biotechnology. He published more than 85 articles (including book chapters and reviews) on antibody engineering and phage display. He is the scientific coordinator of the EC FP7 funded project AntibotABE (www.antibotabe.com). He is working on the development of human and human-like antibodies for proteome research, diagnostics and therapy. Another field of work is the identification of immunogenic proteins of pathogens using phage display. He co-founded the mAb-Factory GmbH in 2007 and the Yumab GmbH in 2012.
Geert Vanden Bossche, DVM, Ph.DCo-Founder and CSO, Univac NV, BelgiumGeert Vanden Bossche obtained his DVM at the Veterinary Faculty of Ghent and his PhD in Virology at the University of Hohenheim, Stuttgart. Following his postdoctoral training in virology, immunology and molecular biology at the Free University of Berlin and Hohenheim (Germany), where he subsequently held adjunct faculty appointments, he transitioned to the Vaccine Industry where he served various senior roles in both early and late vaccine development at GlaxoSmithKline Biologicals, Novartis Vaccines & Diagnostics and Solvay Biologicals. He then joined the Bill & Melinda Gates Foundation to serve as SPO in Vaccine Discovery for Global Health. He is founder of UNIVAC llc in the US and UNIVAC NV in Belgium and visiting scientist at the REGA Institute, University of Leuven (Belgium). Geert is board certified in virology and microbiology, the author of over 30 publications, and inventor on several patent applications. He has presented vaccine- and adjuvant-related topics at multiple international congresses.
Max Reynolds, Ph.DManaging Director, 98 Alive Pty Ltd., AustraliaMax Reynolds has over half a century of global experience in scientific research, business and product development. His commitment and determination to exploring biotechnology and discovering new practical uses for it has led to many advances, including the development of 98 Alive Pty Ltd., which is produced by 98 Alive Pty Ltd of which Professor Reynolds is also the Managing Director. He has previously lectured at leading Australian university, Griffith University in Brisbane, Queensland and has held the position of Director of the Program in Australasia Botanical Medicine for Population Health.
Giulio Tarro, Ph.DTemple University College of Science and Techology, USAProfessor Giulio Tarro has been appointed the Editor-in-Chief of Vaccine Research and Development (VRD), an international, peer-reviewed open access journal published by Spring City Culture International Group. Dr. Tarro has been engaged in medical research for over 30 years. He was born on July 9, 1938 in Messina, Sicily, where he attended High School, and in 1956 began his medical studies at Messina University and then in 1960 continued at Naples University from which he received his M.D. "summa cum laude" in 1962 and the professorship for Oncological Virology in 1972. His research work began in 1960 in the virology laboratory of the department of Medical Pathology at the University of Naples and continued during the entire period of his medical studies. In I963 and 1964 he was at the Polyclinic of the University in Naples receiving training in pathology, neurology and internal medicine. In 1965 he went to the Children's Hospital Research Foundation at the University of Cincinnati, where he worked with Dr. Albert B. Sabin as a Research associate for three years and, subsequently, in 1968 and 1969 he was assistant Professor of Research Paediatrics at the same University. From there Dr. Tarro went back to Naples and established a virology laboratory at the Hospital for Infectious Diseases with the help of a Research Contract from the National Cancer Institute (U.S.A.). In 1973 Dr. Tarro worked as Senior Scientist at the Frederick Cancer Research Centre with Dr. Albert Sabin, who was then a special consultant for the National Cancer Institute. His most notable work provided experimental evidence for the association of herpes viruses with cancer of the cervix. Although at first controversial, this work has been carried out by several laboratories using different techniques. Dr. Tarro's researches in Virology have been both basic and mission oriented. His basic researches have been concerned with antigens induced early during the replication cycle of herpes simplex virus (HSV). Specific antibodies were detected by the enzyme-linked immunosorbent assay in the serum of patients affected with certain carcinomas of the head, neck and urogenital tract. His mission-oriented research has dealt with many aspects of various infectious diseases including broncho-pneumonia, encephalitis, cholera, and the diseases caused by different viruses. During 1979 he was engaged in research on an epidemic disease in Naples called the "dark disease". Dr. Tarro isolated the respiratory syncytial virus (RSV) and found antibody evidence that this virus was behind the epidemic. The World Health Organization expert were called in and agreed most cases of disease were caused by RSV. In 1981 he suggested the proper use of interferon to cure the cytomegalovirus infection affecting the pope John Paul the second who underwent long surgical operation and received huge blood transfusion after the killing attempt. Dr. Tarro is currently engaged in scientific research related to the separation and identification of tumour antigens present on cell membranes and their potential value in immunotherapy for cancer. He has shown that specific soluble antigens may be used in various tests for a further understanding of their role in various cancer systems. Another study has involved the identification, isolation and characterization of specific virus-induced tumour antigens, which were the "finger-prints" left behind in tumours induced in man by human herpes viruses. Intramural activities have included being director of thesis and research for many candidates; director of medical research fellowships for medical students; participation in research planning for clinical colleagues; teaching virology, oncology and immunology to medical and graduate students. He is on the editorial board of various Italian medical journals. Dr. Tarro has been elected to membership of many academies and societies. He has also been the recipient of many awards and honours. Dr. Tarro is life president of the T. and L. de Beaumont Bonelli Foundation for Cancer Research officially recognized by Italian presidential decree n. 36 of January 3, 1978. The aim of the Foundation is the promotion of scientific research on cancer and was instituted thanks to the generous donation of the late Teresa Berger who left to the foundation a large part of her patrimony, whereas the late husband, the Earl Luigi de Beaumont Bonelli, left most of his patrimony to the Nobel foundation. Dr. Tarro became Division Chief of Virology (1973-2003), and then Department Chief of Diagnostic Laboratories (2003-2006), D. Cotugno Hospital for Infectious Diseases, Naples; Emeritus, 2006. He was the Scientific Coordinator of extracorporeal hyperthermia in HCV patients, First Circle Medicine, Minneapolis (2000-2003). Since 2007 he is Chairman Committee on Biotechnologies and VirusSphere World Academy Biomedical Technologies, UNESCO, and Adjunct Professor Department Biology Temple University College of Science and Techology, Philadelphia, USA.
2017 (November) : 21st World Congress and Exhibition on Vaccines, Vaccination, and Immunization (Vienna, Australia)
https://www.alliedacademies.org/conference-abstracts-files/translational-vaccinology-a-myth.pdf
2021-09-capture-alliedacademies-org-conference-abstracts-files-translational-vaccinology-a-myth.pdf
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Dr. Geert Vanden Bossche of German Center for Infection Research (DZIF), Germany
Session : "Translational Vaccinology: A myth? "
Geert Vanden Bossche obtained his DVM at the Veterinary Faculty of Ghent and his PhD in Virology at the University of Hohenheim, Stuttgart. Following his Postdoctoral training in Virology, Immunology and Molecular Biology at the Free University of Berlin and the University of Hohenheim (Germany), he was given the Venia Legendi and subsequently held adjunct faculty appointments at the University of Hohenheim (Germany), the University of Leuven (Belgium) and the European Faculty for Environmental Sanitation at the University of Ghent (Belgium). He then transitioned to the Vaccine Industry to serve various senior roles in both early and late vaccine development (GSK, Novartis, Solvay). In 2008, he joined the Bill & Melinda Gates Foundation in Seattle to serve as Senior Program Officer in Vaccine Discovery for Global Health. Furthermore, he also founded UNIVAC LLC, a start-up vaccine company, and coordinated the Ebola Vaccine Program on behalf of GAVI. He is now the Head of Vaccine Development Office at the German Center for Infection Research (DZIF) in Germany. He is board certified in Virology and Microbiology, the author of over 30 publications, and inventor on a patent application for universal vaccines. He has presented vaccine- and adjuvant-related topics at multiple international congresses.
2021 (Sep 20, 21) - Vaccine Summit, Washington DC
https://scientiameetings.com/conferences/vaccines/speakers
2021 (Sep) capture from celebritynews.pk : "Geert Vanden Bossche Pics, Wikipedia, Biography"
https://celebritynews.pk/geert-vanden-bossche/
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Geert vanden bossche wikipedia : [ No Wikipedia exists for this person as of September 26, 2021 ]
Geert Vanden Bossche is an independent virologist and vaccine expert.
He has previously been employed by the likes of GAVI and The Bill & Melinda Gates Foundation.
With his open letter being circulated on the internet, some are curious to know more about him.
Vanden Bossche studied at Ghent University for his M.D. in Veterinary Medicine from 1980 to 1983.
He then obtained his Postdoctoral training in Equine Medicine and Surgery at the Free University of Berlin (1984-1987).
From 1990, Vanden Bossche underwent a Postdoctoral Fellowship in Virology at James A. Baker Institute for Animal Health, Cornell University in New York.
He was board certified in Veterinary Virology in 1990.
Two years later he was Board certified in Veterinary Microbiology and Animal Hygiene.
Some of the other universities where Geert Vanden Bossche has worked as an academic include the Robert Koch Institute in Berlin, the University of Hohenheim in Stuttgart, the REGA Institute, KU Leuven in Belgium.
[...]
On 6 March 2021, Geert Vanden Bossche shared his open letter to the World Health Organisation (WHO) to Twitter.
He states: “In this agonizing letter I put all of my reputation and credibility at stake.”
You can read the full open letter and follow-up statement on https://twitter.com/GVDBossche/status/1368232172872732675
Geert Vanden Bossche DVM PhD has sounded an alarm to the WHO and others that the global mass covid vaccination program may drive an ever greater number of mutations of SARS-CoV-2 leading to ‘immune escape’ and escalating deaths and illness
Dr Vanden Bossche is convinced we are currently witnessing the calm before the storm – suggesting that the next wave will be much more dramatic than the last two
Dr Vanden Bossche is promoting an emerging NK cell-based vaccination technology, with which he has a 10-year research background, in place of the novel antigen-based vaccines that are being rolled out globally
Geert Vanden Bossche received his DVM from the University of Ghent, Belgium, and his PhD degree in Virology from the University of Hohenheim, Germany.
He held adjunct faculty appointments at universities in Belgium and Germany.
After his career in Academia, Geert joined several vaccine companies (GSK Biologicals, Novartis Vaccines, Solvay Biologicals) to serve various roles in vaccine R&D as well as in late vaccine development.
Geert then moved on to join the Bill & Melinda Gates Foundation’s Global Health Discovery team in Seattle (USA) as Senior Program Officer; he then worked with the Global Alliance for Vaccines and Immunization (GAVI) in Geneva as Senior Ebola Program Manager.
At GAVI he tracked efforts to develop an Ebola vaccine.
He also represented GAVI in fora with other partners, including WHO, to review progress on the fight against Ebola and to build plans for global pandemic preparedness.
Back in 2015, Geert scrutinized and questioned the safety of the Ebola vaccine that was used in ring vaccination trials conducted by WHO in Guinea.
His critical scientific analysis and report on the data published by WHO in the Lancet in 2015 was sent to all international health and regulatory authorities involved in the Ebola vaccination program.
After working for GAVI, Geert joined the German Center for Infection Research in Cologne as Head of the Vaccine Development Office.
He is at present primarily serving as a Biotech/ Vaccine consultant while also conducting his own research on Natural Killer cell-based vaccines.
https://www.newspapers.com/image/733590642/?terms=%22geert%20Vanden%20bossche%22&match=1
https://www.vet.cornell.edu/departments-centers-and-institutes/baker-institute
https://olis.oregonlegislature.gov/liz/2021R1/Downloads/FloorLetter/3165
2021-oils-oregonlegislature-gov-downloads-floor-letter-desk-of-senator-boquist-geert-vanden-bossche-phd-indep-researcher.pdf
https://www.omicsonline.org/open-access/rethinking-vaccinology-act-universally-think-nk-cells.pdf
saved PDF ...
Review Article Open Access
Re-thinking Vaccinology: “Act Universally, Think NK Cells”?
Geert Vanden Bossche*
Head of Vaccine Development Office, German Center for Infection Research, University Clinic Cologne, Belgium
*Corresponding Author:
Geert Vanden Bossche
Head of Vaccine Development Office
German Center for Infection Research
University Clinic Cologne
Joseph- Stelzmann-Str. 9b, D-50931 Cologne, Belgium
E-mail: geert.vandenbossche@live.be
Received date: August 05, 2017; Accepted date: August 23, 2017; Published date: September 7, 2017
Citation: Vanden Bossche G (2017) Re-thinking Vaccinology: “Act Universally, Think NK Cells”?. J Mol Immunol 2:112.
Copyright: © 2017 Vanden Bossche G. This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
Visit for more related articles at Journal of Molecular Immunology
Abstract
Traditional and modern vaccines that are currently licensed for commercial use have proven safe and effective in fighting several infectious diseases; they are unquestionably among the most efficient tools for promoting individual, public and global health. However, the vaccine field is still facing important shortcomings in that the use of vaccines has not been successful yet in preventing many other, especially chronic, infectious diseases and that a therapeutic effect remains beyond reach of contemporary vaccines. As vaccine-mediated immune protection is widely acknowledged to result from the combined effect of specific target antigens and nonspecific immune stimulating agents, it is likely that limitations of conventional vaccinal antigens and adjuvants are responsible for these shortcomings.
This article aims at highlighting weaknesses in traditional vaccinology and calls for novel approaches to immune intervention to address those flaws and overcome the single-most important challenge in vaccinology, namely immune escape.
Keywords
Vaccinology; NK cells; Infectious diseases; Immune protection
Limitations of Conventional Target Antigens Used in Traditional/Contemporary Vaccines
To eliminate safety risks related to infectivity inactivated pathogens and, more suitably, well-characterised subunit or recombinant pathogen-derived antigens have increasingly been used as immunogens in ‘modern’ vaccines. Recombinant protein antigens can either be synthesised in vitro or in vivo (the latter as in case of nucleic acid-based vaccines, for example). The selection of vaccinal antigens/ epitopes is usually based on their capacity to induce functional immune responses that correlate with protection upon natural infection. This is to say that the vast majority of modern vaccines are designed at recapitulating naturally induced immune responses that correlate with protection against infection or disease. Consequently, target antigen (Ag) ‘discovery’ tends to concentrate on specific, naturally immunodominant epitopes that are expressed on the outer surface of free-circulating pathogens (hereafter called ‘B cell [Bc] target epitopes’) or on the surface of infected or diseased host cells within the context of MHC class I (hereafter called ‘T cell [Tc] target epitopes’). Both types of epitopes may be subject to antigenic change whereas their specific recognition is directly (e.g., in case of Tc target epitopes) and/or indirectly (e.g., due to T help-dependence of antibodies or effector T cells) restricted by the MHC background of the host. The more stringently the immune recognition of cognate T help (Th) epitopes is MHC class II-restricted, the higher the specificity with which a target epitope is recognised. It is reasonable to assume that the higher the level of specificity of target epitope recognition, the higher the likelihood for a pathogen to escape the host immune response.
Prophylactic anti-viral or anti-bacterial vaccines, for instance, primarily rely on the induction of functional but strain-specific antibody (Ab) responses to Bc epitopes. To broaden the immune response, multiple Bc and/or Tc target epitopes can be combined in one and the same vaccine (so-called ‘multivalent’ vaccines). However, such combinatorial approaches often result in manufacturing complexity and issues of immunodominance hierarchy of immune responses to the different valences used. Although capable of preventing extracellular spreading microbes from reaching their tissuespecific target cells or organ-specific target tissues and thus, preventing them from causing systemic infection or disease, antibodies (Abs) cannot usually eliminate infected or diseased host cells. Although cytotoxic Abs (e.g., antibody-dependent cell-mediated cytotoxicity [ADCC] Abs) do have the potential to kill infected or diseased host cells, their maturation and persistence is likely to require persistent antigenic stimulation or repeated boosting [1,2]. The benefit, therefore, of contemporary Ab-based vaccines (so-called ‘Bc vaccines’) is largely limited to prophylactic immune intervention in diseases caused by extracellularly spreading microbial toxins or by infectious pathogens that are decorated with protective antigens and disseminate into the bloodstream to reach their target tissue or tissue-specific target cells. Immune subversive antigens (e.g., allergens or tumorigenic antigens) as well as infectious pathogens that are decorated at their surface with self-mimicking components (e.g., certain parasites) or propagate via cell-to-cell transmission or lymphatic trafficking of infected, mucosalresident dendritic cells (e.g., certain viruses ) largely remain beyond reach of contemporary vaccines. Mucosal Abs (i.e., IgA) as, for example, induced by live attenuated vaccines, or high titres of systemic Abs (i.e., IgG) may enable protection against local infection with certain infectious pathogens by neutralising these pathogens at the portal of entry. Live attenuated vaccines may, however, be hazardous in that they can occasionally cause debilitating disease when vaccine virus reverts or recombines to form virulent virus, as observed in some rare cases of immunisation with OPV [3,4]. In addition, Abs directed at Bc epitopes exposed on the surface of pathogens are often strain-/ serotype-specific (see above). Hence, minor changes in pathogen-encoded Bc target epitopes, for example due to spatial rearrangements (i.e., in case of conformational epitopes) or a spontaneous genetic mutation or recombination, may already suffice for the pathogen to escape a previously naturally induced or vaccine-mediated Ab response. Ab-based vaccines may, therefore, fail to induce protection against distinct, although phylogenetically related, pathogen strains/ serotypes. In addition, immune recognition of cognate T help (Th) epitopes may be poor or lacking in a subset of vaccine recipients (socalled ‘non-responders’) due to MHC polymorphism, thus resulting in the absence of functionally protective Ab responses. Due to the abovementioned limitations, pathogens may succeed in escaping the host immune response and preserve their fitness. Although immune escape can to some extent be mitigated by enhanced T help through coformulation of antigen with adjuvant, vaccine adjuvantation does not come without risk of side effects (see below). Last, to ensure adequate Ab isotype switching and high, long-lasting titres of protective Abs against surface-exposed proteins or other protein-conjugated antigens (e.g., polysaccharides), traditional prophylactic, non-live vaccines usually require one or more booster doses. To enable targeting of epitopes that are expressed on infected or diseased cells, new vaccine candidates frequently also comprise conserved linear peptide epitopes that are presented on MHC class I molecules (hereafter called ‘Tc target epitopes’). However, immune recognition of these epitopes is contingent on their specificity to the polymorphic MHC haplotype background of the host. This already implies that conserved Tc target epitopes will only be protective in individuals who are already genetically predisposed to Tc-mediated pathogen control by virtue of expression of MHC alleles matching the specificity of these epitopes (so-called ‘protective’ MHC alleles) [5]. In order to broaden the spectrum of effector Tc responses, multiple Tc target epitopes can be incorporated into vaccines. Multi-epitope vaccines can, for example, be produced by using sophisticated nucleic acid technology or recombinant viral or bacterial vectors. However, similarly to the situation described above for Bc target epitopes, the induction of fullfledged immune responses toward multivalent pathogen-encoded Tc epitopes requires booster injections (or ‘prime-boost’ regimens) whereas immune escape issues remain due to immune dominance hierarchy (i.e., resulting in suboptimal immune responses to certain Tc epitopes) or because of MHC-restriction of helper or effector T cells or spontaneous or vaccine-mediated mutation of immunodominant Tc epitopes (a phenomenon called ‘immune pressure’). Hence, multiepitope Tc vaccine candidates have not been effective in inducing broad and long-lasting immune protection in target populations with a heterogeneous MHC background.
Notwithstanding the nature of their target epitopes, traditional nonlive vaccines require adjuvantation and inclusion of MHCII-binding antigenic determinants (hereafter called ‘Tc helper epitopes’) to induce cognate T helper cells that can assist priming of effector B cells or MHCI- restricted T cells. Traditional pro-inflammatory adjuvants/ immune potentiators may, however, cause local reactogenicity and raise safety concerns. Hence, regulatory hurdles to the use of adjuvants in vaccines, especially if their use is unprecedented (e.g., other than Alum), may be substantial. Traditional Th2 adjuvants (e.g., Alum, oilin- water emulsions) are most commonly used to enhance humoral Ab responses whereas Th1 adjuvants (e.g., Pathogen Associated Molecular Patterns [PAMPs]) are regularly used to enhance T cell-mediated effector responses. However, alike Tc target epitopes, Tc helper epitopes are subject to MHC-restriction. To overcome absence of natural Th2 epitopes or mitigate limitations of cognate type 2 T help that are due to immunogenetic restriction, Bc target epitopes can be conjugated to a conserved promiscuously MHCII-binding Th peptide or to a protein comprising one or more promiscuous Th peptides (e.g., tetanus toxoid, diphtheria toxoid or a non-toxic mutant of diphtheria toxin [e.g., CRM197]) as in case of multivalent conjugate vaccines (e.g., glycoconjugate vaccines). Likewise, limitations due to immunogenetic restriction of cognate type 1 T help can be mitigated by co-localisation of Tc target epitopes and promiscuous Th peptide(s) to the same protein/polypeptide Ag. Alternatively, co-localisation of Tc target epitopes to multiple cognate MHCII-restricted Th peptides (as in case of multivalent polypeptide or nucleic acid-based Tc vaccines) combined with concomitant provision of type 1 immune stimulatory signals (e.g., via co-formulation with immune potentiating nucleic acid sequences or other PAMPs) may equally lead to enhanced breadth of Tc target epitope recognition by MHC class I-restricted effector T cells. Cognate T help facilitated by Th1 or Th2 adjuvants tends to broaden immune recognition of MHCI-restricted Tc epitopes or specific Bc epitopes, respectively. Promiscuously MHCII-binding Th peptides are ideally suited to broaden T help across a broad spectrum of MHCII haplotypes. Based on observations from natural infection, it cannot be ruled out, however, that the combination of promiscuous helper peptides and adjuvants is at risk of causing immune pathology, for example by promoting priming of autoreactive T cells (see also below under ‘Limitations and risks associated with the use of adjuvants in vaccines’).
Limitations and Risks Associated with the Use of Adjuvants in Vaccines
To mitigate limitations due to the high level of specificity and/ or immunogenetic restriction of Ag recognition, traditional vaccinology has been largely relying on the use of several different types of adjuvants. Adjuvants primarily enhance the immune response through upregulation of presentation of Ag-MHC complexes on the surface of Ag-presenting cells (APCs), thereby licensing MHCII-restricted T helper cells to assist priming of effector B cells or MHCI-restricted effector T cells Figure 1.
Figure 1: Immunological synapse formation and its role in immune activation of cognate CD4+ T helper cells: CD4+ helper T cells mature and activate APCs through recognition of epitopes presented by class II MHC molecules [MHC II] and interaction of CD40 and CD40 ligand [CD40L]. The CD40-CD40L interaction causes the APC to upregulate expression of costimulatory molecules such as CD80 and CD86 and to secrete cytokines IL-12 and IL-15. The costimulatory molecules interact with CD28 on the CD8+ CTL to provide a second CTL activation signal in addition to T cell receptor [TCR] recognition of an antigenic peptide presented by a class I MHC molecule [signal 1]. IL-12 also contributes to activating the CTL and polarising the T helper cell to produce Th1 cytokines, such as IFN-γ. IL-15 contributes to induction and maintenance of CTL memory and longevity. Regulatory T cells, including NK T cells and CD25+CD4+ T cells, can dampen or inhibit the CTL response in order to prevent autoimmunity, but also reduce the immune response to the vaccine. Various strategies may be employed to improve the natural T cell response. Epitope enhancement of class I or class II MHC-binding peptides can increase their affinity for the respective MHC molecules and their immunogenicity (from: “Progress on new vaccine strategies against chronic viral infections.
Limitations of Th2-Adjuvanted Vaccines
Conventional purified (e.g., recombinant/ subunit) pathogenderived Ags comprising one or more Bc target epitopes have been combined with type 2 T help-activating adjuvants (e.g., Alum, oil-inwater emulsion etc.) to enhance their immunogenicity. Th2 polarisation of vaccine-induced immune responses results from adjuvant-mediated triggering of Th2 cytokine secretion (e.g., IL-4, IL-5, IL-6). Th2 adjuvant-mediated upregulation of Th epitopes enhances immune recognition of Bc target epitopes that are associated with these Th epitopes (via a so-called ‘cognate’ mechanism of immune recognition). This increases the breadth of the Ab response in a way that promotes immune recognition of a more diversified spectrum of Bc epitopes across a set of heterologous pathogen strains (a phenomenon called ‘epitope spreading’). It is, however, reasonable to assume that epitope spreading is able to induce changes in the hierarchy of immune responses to pathogen-specific vaccinal epitopes. This may result in diminished recognition of so-called ‘protective’ Bc epitopes (i.e., Bc epitopes that are of vital importance to the pathogen), thus promoting immune escape of the target pathogen. On the other hand, nonAg-specific type 1 stimulation of CD4+ bystander T cells may occasionally lead to stimulation of noncognate B cells, thereby posing a risk of inducing allergic humoral immune responses towards pathogen- or even nonpathogen-related vaccine components [6-8].
Formulation of conformational Bc epitopes on Alum or their coformulation with other particulate adjuvants (e.g., emulsions, liposomes) may also lead to spatial rearrangements and, therefore, elicit Abs that do not match the natural antigenic conformation of these epitopes. This not only allows the pathogen to escape vaccineinduced immune responses but could possibly even raise safety concerns related to an increased likelihood of vaccine-mediated exacerbation of disease upon natural, post-immunisation exposure to certain viral pathogens [9-11].
Limitations of Th1-Adjuvanted Vaccines
To enhance cell-mediated immune responses towards target pathogens, contemporary vaccine approaches increasingly combine conventional pathogen-derived epitopes with type 1 T help-activating adjuvants (‘Th1 adjuvants’). Th1 adjuvants mostly mimic natural innate immune modulators (i.e., PAMPs comprising TLR agonists such as lipopolysaccharide, lipoproteins, lipopeptides, flagellin, doublestranded RNA, unmethylated CpG). Depending on their formulation and use in mutually synergising combinations, PAMPs may also induce Th17 immune signalling [12]. In case of protein-based vaccines, physical or chemical binding of the adjuvant with the vaccinal protein antigen is critical to ensure optimal biological activity. The ‘success’,therefore, of traditional Th1 adjuvants typically requires sophisticated conjugation technology or formulation with a macromolecular or particulate carrier (e.g., emulsions, liposomes, VLPs) capable of binding both, the vaccinal protein (or protein-conjugated) antigen and the adjuvant. Alternatively, Th1-assisted immune responses towards cell-bound target antigens can also be induced upon delivering these antigens as part of a recombinant genetic construct (e.g., by way of viral vectors, DNA-based vaccines, recombinant alpha-virus replicon particles or reassorted viruses) or as nucleic acids (e.g., in form of DNA, RNA or messenger RNA [mRNA]).
Th1 adjuvant-mediated upregulation of Th epitopes mitigates the impact of MHC class II restriction on immune recognition of cognate MHC class I-restricted target epitopes that are co-localised to these Th epitopes. This increases the breadth of the Tc effector response in a way that promotes immune recognition of a more diversified spectrum of Tc epitopes across vaccine recipients with a heterogenous MHC background (so-called ‘epitope spreading’). However, the resulting changes in the hierarchy of immune responses to vaccinal Tc epitopes may lead to poor or deficient recognition of ‘protective’ MHCIrestricted pathogen-specific Tc epitopes, thus enabling the target pathogen to escape vaccine-mediated cellular immune responses. On the other hand, nonAg-specific type 1 stimulation of bystander T cells could occasionally lead to stimulation of noncognate effector cells, thereby posing a risk of inducing autoreactive immune responses towards certain tissue-specific self-antigens [13-16].
Given the occasional observation of autoimmune responses in association with natural infection (e.g., certain viral infections), it is also conceivable that co-formulation of strong adjuvants (e.g., Th1 or Th17 adjuvants) with specific pathogen-derived promiscuously MHCII-binding Th peptides (PPPs), or proteins comprising such peptides, promotes Tc-mediated recognition of self-peptides that share homology in amino acid composition with said specific PPPs. Such autoreactive responses are likely to be triggered by ‘degenerate specificity of TCR-mediated recognition’, also called ‘TCR degeneracy of immune recognition’ [17-20]. The author postulates that this phenomenon could also occur as a result from adjuvant-mediated enhancement of PPP presentation on APC surface-expressed MHCII molecules.
In conclusion, immune responses induced by traditional vaccines are specifically directed to a limited number of immunodominant epitopes and restricted by the MHC background of the vaccine recipient. As a result, pathogens may escape vaccine-induced humoral and/or cellular host immune responses, thereby preventing vaccines from providing the target vertebrate population with broad and longstanding protection against target pathogens. Despite their capacity to successfully prevent systemic infection or disease caused by one or more (the latter, for example, in case of multivalent vaccines) specific pathogens, current Ab-based vaccines, for example, do not usually provide significant cross-protective immunity and may even fail to protect a subset of vaccine recipients (so-called ‘non-responders’). On the other hand, T cell-based vaccines targeted at cell-bound pathogenic antigens primarily protect individuals that are already naturally predisposed to T cell-mediated pathogen control by virtue of their expression of protective MHC or TCR alleles. Hence, the protective effect of T cell-based vaccine candidates in controlling infection or disease strongly depends on the immunogenetic background of the vaccine recipient.
Even ‘modern’ sophisticated vaccine constructs, for example comprising multiple Bc and/or Tc target epitopes combined with (promiscuous) T helper peptides and/ or adjuvants, are basically still mimicking naturally induced immune responses. This already explains why vaccines have failed to induce long-lasting, broadly and universally protective immunity and may ultimately allow the pathogen to escape from the host immune system. Because adjuvantation of vaccines may lead to changes in immunodominance hierarchy between the selected vaccinal epitopes, adjuvants are at risk of enabling protective vaccinal epitopes to evade vaccine-induced immune responses. This would particularly apply to situations where multi-epitope constructs co-formulated with adjuvants are used for mass vaccination campaigns or routine immunisation programs.
NK Cell-Based Immunotherapy and Vaccines: The New Holy Grail in Modern Immune Intervention?
Based on all of the above, there is an obvious medical need for vaccinal antigens that are truly and universally protective in that they are capable of educating the host immune system to mount a type of protective immune response which the target pathogen is unable to escape from.
In this regard, NK cell-based immune interventions are causing a great deal of excitement and have strengthened the belief that NK cells can effectively contribute to fighting infectious diseases or controlling cancer. Natural killer cells (NK cells) are, indeed, widely renowned for their role in eliminating virus-infected as well as damaged and malignant (i.e., transformed) cells very efficiently [21]. They are characterised by a thin line of discriminative capacity of ‘self ’ as compared to ‘non-self ’ and by their innocuity towards healthy host cells. Their cytotoxic action is balanced by signalling through patternrecognition receptors on the NK cell surface. These receptors serve an NK activating (e.g., via monomorphic NKG2D and NKp46 in man and mice, respectively) or inhibitory role (i.e., via family of polymorphic KIRs and Ly49 receptors in man and mice, respectively). By virtue of their MHC class I-specific inhibitory pattern recognition receptors, NK cells are capable of detecting and killing cells that have lost cognate self MHC class I-educating ligands [22,23]. In addition, the expression on target cells of ligands recognised by activating NK receptors (e.g., NKG2D and NKp46) serves as another important checkpoint for NK cell activation and induction of their cytolytic activity and cytokine production [24,25].
Germline-encoded activating NK cell receptors (NCRs) recognise aberrant expression of self-specific ligands on autologous cells. They sense alterations in expression patterns of self-ligands expressed on transformed, stressed or infected host cells [13,26]. NK cells use a diversified array of these activating NK cell receptors to detect changes in their environment and respond to alterations caused by transformation, cellular stress or infection. NK cells can also respond to specific antigens by receptors that are seemingly required for Agspecific recognition (e.g., NKG2C, NKG2D). However, the interaction between such specific antigens and activating receptors on NK cells cannot explain antigen-specific features of the immune response. This already suggests that interactions between specific antigenic ligands and receptors on NK cells do not require these ligands to display a specific antigenic sequence but rather enable sensing of ‘incompatible’ ligands [13,27]. Such incompatibility might be due to aberrant or unfavourable binding of antigenic ligands to cognate self MHC class I molecules. The idea that NK cells could be endowed with an alternative ligand-sensing system could also explain their capacity to recognise a broad and highly diversified spectrum of antigen patterns. It has repeatedly been reported that NK cells can be primed and educated to acquire memory if they are activated by sensitising signals that are delivered in the absence of activation of inhibitory MHCI- specific receptors [28]. Co-activation resulting from the loss of inhibitory control is thought to lower the activation threshold of NK cells for responding to a diversified range of virus-, tumour- or stress-derived signals or ligands. The resulting enhancement of NK cell-mediated responsiveness towards these ligands is thought to rely on several different mechanisms [29]:
Confined compartmentalisation of activation receptors (e.g. NKp46) in signalling microclusters/ nanodomains at the immune synapse.
Enhanced expression on NK cells of adhesion molecules (e.g. lymphocyte function-associated antigen 1, also known as LFA-1) that enable stable conjugate formation.
Down-regulated expression of inhibitory receptors specific for self MHCI molecules.
Meanwhile, several studies provide compelling evidence of antigenspecific recall responses of memory NK cells but the molecular interactions between NK cell receptors and cognate pathogen-derived antigens that underlie these responses are still largely unknown [30,31]. Scientists increasingly acknowledge that an improved understanding of the mechanisms that enable durable antigen-specific immune recognition by a diversified spectrum of memory NK cells may unleash the immunological and clinical potential of NK cell-based immunotherapies and even pave the way to NK cell vaccines that could help defeat infectious, immune-mediated or tumour diseases. The idea that NK cells could be endowed with an alternative ligandsensing system is particularly intriguing and may require the scientific and medical community to re-think approaches to investigate or exploit NK cell triggering. Unlike recognition of pathogen-derived target antigens used in traditional vaccines, NK cell-mediated recognition of pathogen-derived antigens that are reminiscent of ‘self ’ (so-called ‘altered self ’ antigens) is not MHC-restricted in that these cells recognise antigens regardless of the immunogenetic background of the host, sometimes even across phylogenetically unrelated host vertebrate species (hence called ‘universal’ vaccines). There is a particular medical need to better explore and exploit immunisation strategies that harness NK cells to acquire adaptive immune features and enable improved vaccines or immunotherapeutic approaches capable of eliminating infected or pathologically altered or transformed host target cells. As NK cells naturally serve a selfprotective function, more research into pathogen-derived immune subversive antigens that bear the hallmarks of ‘self ’ is warranted. An improved understanding of the role of pathogenic self-mimicking antigens combined with better insights in the immune pathogenesis of infectious or immune-mediated diseases would enable a more rational design for modern immune interventions. Novel, NK cell-based vaccines would ideally be capable of teaching these innate immune cells to mount a full-fledged adaptive immune response towards immune subversive antigens that deviate from ‘self ’.
It is reasonable to assume that immune interventions that have the capacity to prime NK cells into long-lived, effector memory cells which universally recognise a broad spectrum of pathogens, even across phylogenetically unrelated strains or species, would greatly contribute to the prevention or control of multiple infectious, immune-mediated or oncogenic diseases in naturally susceptible vertebrate species. Such broadly and universally protective vaccines would be highly costeffective and obviate the need for developing personalised vaccines,which would be prohibitively expensive and difficult to implement in most parts of the world.
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Proc Natl Acad Sci U S A
. 2003 Dec 9;100(25):15011-6. doi: 10.1073/pnas.2336091100. Epub 2003 Nov 25.
Natural killer cells in HIV-1 infection: dichotomous effects of viremia on inhibitory and activating receptors and their functional correlates
Domenico Mavilio 1, Janet Benjamin, Marybeth Daucher, Gabriella Lombardo, Shyam Kottilil, Marie A Planta, Emanuela Marcenaro, Cristina Bottino, Lorenzo Moretta, Alessandro Moretta, Anthony S Fauci
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PMID: 14645713
PMCID: PMC299884
Free PMC article
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Proc Natl Acad Sci U S A. 2004 Apr 20;101(16):6326
Abstract
Natural killer (NK) cells play a central role in host defense against various pathogens. Functional defects of NK cells in HIV-1 infection as a direct effect of abnormal expression or function of inhibitory NK receptors (iNKRs), activating natural cytotoxicity receptors (NCRs), and NKG2D have not yet been described. This study demonstrates an expansion of the functionally defective CD56-/CD16+ population of NK cells in viremic versus aviremic patients. We also demonstrate that in HIV-infected viremic patients, expression of iNKRs was well conserved and that in most cases, there was a trend toward increased expression on NK cells as compared with healthy donors. It was also demonstrated that the major activating NK receptors, with the exception of NKG2D, were significantly down-regulated. In contrast, the expression of iNKRs and activating receptors in HIV-infected individuals whose viremia was suppressed to below detectable levels by highly active antiretroviral therapy for 2 years or longer was comparable to that of healthy donors. Functional tests confirmed that the abnormal expression of the activating receptors and of iNKRs was associated with a markedly impaired NK cytolytic function. This phenomenon is not attributed to a direct HIV-1 infection of NK cells; thus, this study may provide insight into the mechanisms of impaired host defenses in HIV-1 viremic patients.
https://pubmed.ncbi.nlm.nih.gov/14645713/