Antibodies are a vital component of the immune system required for protection and control of infectious diseases. Beyond the traditional mechanism of neutralisation of pathogens (inhibition of the pathogen from infecting a cell), antibodies can act as beacons - instructing the innate immune system on how to attack and eliminate pathogens. 

Our lab aims to apply cutting-edge high throughput experimental technologies, matched with computational analysis, to examine how these functional antibodies work, which will provide important insights to improve antibody-based vaccines and therapies. We currently have projects exploring antibody responses against a range of infectious diseases including HIV, Mycobacterium Tuberculosis, Malaria, Influenza and as well as the pathogenic role of antibodies in Autoimmune Diseases including Sjogrens and ARF.

The Dynamic and Diverse Complexity of Antibody Responses. The functional capacity of the humoral (Antibody) immune response is determined by complex biophysical antibody features including (panel 1) the ability of the antibody to recognise the pathogen, (panel 2) the structure of the antibody's Fc region, which in turn can modulate the antibodies capacity to engage with (panel 3) Fc receptor/immune molecules and (panel 4) availability of the Fc receptors on different effector cells/immune molecules in the surrounding environment. 

Collectively, all these factors then dictate the functional antibody immune response induced

Arnold K.B. and Chung A.W. Prospects from Systems Serology Research. Immunology. 2018. 

Mycobacterium tuberculosis (Mtb) infects approximately one third of the world’s population and is currently one of the major causes of morbidity and death worldwide. The role of antibodies in Mtb is underexplored, although rare studies suggest that antibodies may contribute to Mtb control. Studies by our lab suggest that patients that can control Mtb (latently infected) have improved functional antibody responses compared to symptomatic (active) Mtb patients. Therefore, we are interested in characterising the antibodies from patients with different clinical Mtb disease outcomes in order to further understand the importance of these potentially protective antibodies.

Autoimmune diseases, including more than 100 known pathologies with various manifestations, concern 5-8% of the population worldwide and are responsible for an important burden in terms of morbidity, mortality and healthcare costs. Some autoimmune diseases are organ-specific (such as type 1 diabetes) whereas others are systemic (i.e. able to affect any system in the body), but they all have in common the dysregulation of the immune system.

Among the systemic autoimmune diseases, Sjogren’s syndrome is the 2nd most common (0.01-0.3% of the adult population) but still faces unmet diagnostic, therapeutic and follow-up needs. Inflammatory infiltration of the salivary and lacrimal glands responsible for dry eyes and mouth is the main feature of Sjogren’s syndrome, but apart from this classical feature, the clinical spectrum is broad (e.g. rheumatologic, neurologic, bronchiolar, pulmonary, haematological or renal manifestations…).

As all systemic autoimmune diseases, Sjogren’s syndrome has a complex pathophysiology, but what is commonly accepted nowadays, is that B cell activation seems to have a pivotal pathological roleas illustrated by the production of many autoantibodies in patients. Hence, we are interested in deeply characterising the autoreactive humoral response from patients with different phenotypes in order to improve our understanding of the pathological mechanisms at work. We think that these new elements should allow the identification of new biomarkers, therapeutic targets and/or subsets of patients, which will be very useful in addressing the main pitfalls in Sjogren’s syndrome management.

Major Collaborators and Co-supervisors of current graduate students:

Stephen Kent - Dept of Microbiology and Immunology, University of Melbourne, Doherty Institute

Stephen Rogerson- Dept of Medicine- University of Melbourne, Doherty Institute

Australian Collaborators

Keith Chappell, Daniel Watterson, Paul Young- University of Queensland

Nigel Curtis - Murdoch Children's Research Center, University of Melbourne

Laura Downie - Dept of Optometry and Vision Sciences, University of Melbourne

Justin Denholm - Victorian TB Program, Melbourne Health, Doherty Institute

Mark Hogarth - Immune Therapies Group, Burnet Institute

Jennifer Juno - Dept of Microbiology and Immunology, University of Melbourne, Doherty Institute

Katherine Kedzierska -Dept of Microbiology and Immunology, University of Melbourne, Doherty Institute

Anthony Kelleher- Kirby Institute, University of New South Wales

Bao Nguyen - Dept of Optometry and Vision Sciences, University of Melbourne

Nichollas Scott - Dept of Microbiology and Immunology, University of Melbourne, Doherty Institute

Kasha Singh - VIDS, Doherty Institute

Wai Hong Tham- WEHI

Adam Wheatley- Dept of Microbiology and Immunology, University of Melbourne, Doherty Institute

Bruce Wines - Immune Therapies Group, Burnet Institute

International Collaborators

Kelly Arnold- Biomedical Engineering, University of Michigan

Blake Ball - University of Manitoba, National Laboratory for HIV Immunology, National HIV and Retrovirology Laboratories, Public Health Agency of Canada

Nikki Moreland- Molecular Medicine and Pathology, University of Auckland

Shelby O'Connor- Dept of Pathology and Laboratory Medicine, University of Wisconsin-Madison

Sophie Valkenburg - Division of Public Health Laboratory Sciences, University of Hong Kong

Marit van Gils - Dept of Medical Microbiology, Amsterdam UMC