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How does a vaccine work?
How does a vaccine work?
General and very basic overview of a vaccine
General and very basic overview of a vaccine
Basic Understanding: ALL vaccines spur the production of protective antibodies (triggering an immune response) because they use various methods to expose organisms to a pathogen or foreign agent. However, the diversity in vaccine development makes it difficult to evaluate the most efficient and sustainable method to prevent viral infections and diseases forever.
Video Credit: From ImmunizeBC, https://immunizebc.ca/how-do-vaccines-work
How does an mRNA, DNA, and protein-based vaccine work?
How does an mRNA, DNA, and protein-based vaccine work?
These are only three vaccine development methods. There are so many other vaccine development methods that scientists use and so many new vaccine development methods to come as virology advances!
These are only three vaccine development methods. There are so many other vaccine development methods that scientists use and so many new vaccine development methods to come as virology advances!
An mRNA vaccine is one of the many vaccine-based approaches to cure viruses. mRNA (messenger RNA) contains the instructions for protein synthesis. It is composed of a chain of RNA nitrogen bases (Adenine, Uracil, Guanine, and Cytosine); every three bases, a codon, codes for an amino acid. mRNA vaccines code for a section of the viral capsid (a.k.a., protein coat). When injected into a patient, the mRNA will enter the cell and get translated into viral proteins. The sudden exposure to these foreign viral proteins will trigger an immune response in the body; new antibodies against the foreign viral proteins will be released, making the patient immune to the virus.
A DNA vaccine works similarly, using DNA as the base of carrying instruction for viral protein assembly instead of mRNA. Lastly, a protein vaccine directly exposes patients to a viral protein, requiring no protein synthesis in the cell.
Gilead Sciences, an American biotechnology company, proposed that their drug, Remdesivir, may treat the novel Coronavirus. Remdesivir is an antiviral drug for treating Ebola virus used for the first COVID-19 case in the U.S.. Its large amount of preclinical evidence suggested that it could be used to treat Coronavirus infections. In fact, doctors in China used and tested many antivirals originally designed to treat Ebola and HIV to treat COVID-19 patients. One study published in February by researchers from Gilead Sciences and and the National Institute of Allergy and Infectious Diseases shows that remdesivir inhibits the replication of MERS-CoV in infected monkeys. This drug works by hijacking the replication mechanism of the virus. Remdesivir is a nucleoside analog designed to mimic adenosine (an RNA base), get into the RNA genome of the virus, and inhibit RNA polymerase from adding additional nucleotides for viral replication. As a result, the virus will not be fully constructed, leaving it unable to infect other cells. Gilead planned to test remdesivir with Chinese health authorities in randomized, controlled clinical trials in February.
Sources (all of above information):
Habibzadeh P, Stoneman EK. The novel coronavirus: A bird's eye view. Int J Occup Environ Med 2020;11:65-71. doi: 10.15171/ijoem.2020.1921
Live Science. "Is there a cure for the new coronavirus?," https://www.livescience.com/can-coronavirus-be-cured.html
StatNews. "An updated guide to the coronavirus drugs and vaccines in development," https://www.statnews.com/2020/03/19/an-updated-guide-to-the-coronavirus-drugs-and-vaccines-in-development/
StatNews. "As the coronavirus spreads, a drug that once raised the world’s hopes is given a second shot," https://www.statnews.com/2020/03/16/remdesivir-surges-ahead-against-coronavirus/
Chemical structure of remdesivir
Image Credit: From American Chemical Society, https://www.acs.org/content/acs/en/molecule-of-the-week/archive/r/remdesivir.html?cid=home_motw
Chemical structures of nucleoside substrate analogues
Image Credit: From MDPI, https://www.mdpi.com/1999-4915/11/4/326
Vaccines help the immune system recognize and attack viruses over a period of time. Typical vaccines contain information for the cell to create an entire virus from scratch. Moderna Therapeutics, a biotechnology company based in Massachusetts, developed a vaccine (mRNA-1273) for treating COVID-19 patients. However, in an attempt to speed up the vaccine creation process, researchers took a few shortcuts: (1) they did not test the vaccine on animals prior to conducting clinical trials, and (2) they took a new approach and created an mRNA vaccine that will instruct cells to create Spike Proteins rather than the entire SARS-CoV-2 virus. The Spike Protein is an important target because it is responsible for binding to cell receptors and fusing with the cell membrane to enhance viral entry. Theoretically, the cell's recognition of the artificially created Spike Protein should trigger an immune response. The body's immune cells should begin fighting the virus after becoming familiar with the Spike Protein structure.
Sources (all of above information):
Live Science. "Is there a cure for the new coronavirus?," https://www.livescience.com/can-coronavirus-be-cured.html
Video Credit: Moderna. "Moderna’s Work on a Potential Vaccine Against COVID-19," https://www.modernatx.com/modernas-work-potential-vaccine-against-covid-19
CanSino Biologics Inc., a biopharmaceutical company headquartered in Tianjin, China, is also working on developing a vaccine for the novel Coronavirus. They are testing a genetically engineered Adenovirus Type 5 Vector (Ad5-nCoV) as a potential vaccine candidate. This vaccine, unlike the one developed by Moderna Therapeutics, is a recombinant vaccine that entwines a small portion of the Coronavirus genome with the genome of an adenovirus (harmless). The replication-defective adenovirus type 5 serves as the vector to deliver the genome of SARS-CoV-2 Spike Protein into the human body. Theoretically, an injected healthy patient should begin producing antibodies against the novel Coronavirus due to their exposure to a small portion of its genome that codes for the Spike Protein.
Source (all of above information):
StatNews. "An updated guide to the coronavirus drugs and vaccines in development," https://www.statnews.com/2020/03/19/an-updated-guide-to-the-coronavirus-drugs-and-vaccines-in-development/
CanSinoBio. "CanSinoBIO’s Investigational Vaccine Against COVID-19 Approved for Phase 1 Clinical Trial in China," http://www.cansinotech.com/homes/article/show/56/153.html
BioSpace. "China’s CanSino Prepares to Advance COVID-19 Vaccine Candidate into Phase II," https://www.biospace.com/article/china-s-cansino-prepares-to-advance-covid-19-vaccine-candidate-into-phase-ii/
The BioNTech company in Germany and the U.S. pharmaceutical company Pfizer are currently creating an mRNA vaccine for COVID-19 which will go into clinical testing in April 2020. Since the vaccine's mRNA holds the instructions for viral protein synthesis, the vaccine should theoretically spur the production of protective antibodies against these foreign viral proteins.
Source (all of above information):
StatNews. "An updated guide to the coronavirus drugs and vaccines in development," https://www.statnews.com/2020/03/19/an-updated-guide-to-the-coronavirus-drugs-and-vaccines-in-development/
Above is a general overview of two different ways an mRNA vaccine could work. A detailed caption of "two categories of mRNA constructs" can be found here.
Above is a general overview of two different ways an mRNA vaccine could work. A detailed caption of "two categories of mRNA constructs" can be found here.
Image Credit: Nature Articles. "The promise of mRNA vaccines: a biotech and industrial perspective," https://www.nature.com/articles/s41541-020-0159-8/figures/1
CurVac's vaccine is also an mRNA-based vaccine that spurs the production of antibodies against SARS-CoV-2. CureVac's mRNA vaccine is supposed to be ready for animal testing by April 2020 and for clinical testing by this summer (2020).
Source (all of above information):
StatNews. "An updated guide to the coronavirus drugs and vaccines in development," https://www.statnews.com/2020/03/19/an-updated-guide-to-the-coronavirus-drugs-and-vaccines-in-development/
Above is an overview of how an mRNA vaccine works on the body
Image Credit: CureVac, https://www.curevac.com/covid-19
GlaxoSmithKline is one of the largest British vaccine manufacturers. It is lending its adjuvants (a substance that enhances the body's immune response to an antigen) to a private company stationed in Chengdu, China, Clover Biopharmaceuticals. Both companies are working on developing a protein-based vaccine to target the ACE2 receptor-binding glycoprotein (S-protein) on SARS-CoV-2. Clover Biopharmaceuticals designed the viral S-Protein trimer using SARS-CoV-2 genomic data. This vaccine exposes the immune system to the pathogenic Spike Protein trimer of SARS-CoV-2, priming it to produce antibodies to act against this significant viral protein responsible for viral entry and fusion.
Source (all of above information):
StatNews. "An updated guide to the coronavirus drugs and vaccines in development," https://www.statnews.com/2020/03/19/an-updated-guide-to-the-coronavirus-drugs-and-vaccines-in-development/
GSK, https://www.gsk.com/en-gb/media/press-releases/clover-and-gsk-announce-research-collaboration-to-evaluate-coronavirus-covid-19-vaccine-candidate-with-pandemic-adjuvant-system/
Inovio Pharmaceuticals, a biotechnology company based in Plymouth Meeting, PA has created a DNA-based vaccine. The DNA codes for a viral protein. Theoretically, injection of the DNA plasmid should generate monoclonal antibody production against SARS-CoV-2 to protect patients from the Coronavirus. There are many advantage of DNA-based vaccines compared to protein-based vaccine (explained in the video at the right). Learn more about Inovio's vaccine approach here.
Source (all of above information):
StatNews. "An updated guide to the coronavirus drugs and vaccines in development," https://www.statnews.com/2020/03/19/an-updated-guide-to-the-coronavirus-drugs-and-vaccines-in-development/
Video Credit: Biotech Primer, https://www.youtube.com/watch?v=BOQ0XsxF02w
Johnson & Johnson, a medical device company based in New Brunswick, NJ is working on a vaccine that exposes patients to a deactivated Coronavirus, priming the immune system to spur the production of protective antibodies. Johnson & Johnson has taken actions against the Ebola and Zika viruses in the past.
Source (all of above information):
StatNews. "An updated guide to the coronavirus drugs and vaccines in development," https://www.statnews.com/2020/03/19/an-updated-guide-to-the-coronavirus-drugs-and-vaccines-in-development/
Sanofi, a pharmaceutical company based in Paris, France, has created effective vaccinations for yellow fever and diphtheria and is currently working with the Biomedical Advanced Research and Development Authority (BARDA) to find a treatment for the novel Coronavirus. Sanofi's approach involves mixing a portion of SARS-CoV-2 DNA with the genetic material of a baculovirus (expression system) to create a chimera (chimera (according to Dictionary.com): DNA molecule derived from two or more different organisms, formed by laboratory manipulation). The baculovirus expression vector system (BEVS) can accommodate large segments of foreign DNA, allowing for the rapid production of recombinant viruses in insect cells (more on baculoviruses here). Exposure to the recombinant DNA (chimera) should theoretically prime the immune system and trigger immediate antibody production against the many viral proteins encoded by the small portion of pathogenic viral DNA.
Source (all of above information):
StatNews. "An updated guide to the coronavirus drugs and vaccines in development," https://www.statnews.com/2020/03/19/an-updated-guide-to-the-coronavirus-drugs-and-vaccines-in-development/
BioSpace, https://www.biospace.com/article/sanofi-to-work-with-barda-on-coronavirus-covid-19-vaccine/
PubMed Articles, https://www.ncbi.nlm.nih.gov/pubmed/29516481
ScienceDirect, https://www.sciencedirect.com/topics/biochemistry-genetics-and-molecular-biology/baculovirus-expression-system
Above is the hepatitis B recombinant vaccine with a bacterial plasmid as the expression system to enable rapid and efficient production of HBV in yeast expression systems.
Image Credit: GenScript, https://www.genscript.com/recombinant-vaccine.html
Regeneron Pharmaceuticals, an American biotechnology company, is using its antibody technologies to find the two most potent antibodies against the novel Coronavirus. They have produced virus-neutralizing antibodies in genetically-engineered mice and isolated antibodies from surviving COVID-19 patients. From their large group of potential antibody candidates, Regeneron will evaluate each antibody's binding affinity to the SARS-CoV-2 Spike Protein and select the top two antibodies to go into clinical testing. By early summer (2020), they hope to begin human testing with their multi-antibody cocktail. Their multi-antibody cocktail therapy serves both as a preventive drug and a treatment drug. In fact, Regeneron created an antibody cocktail during the 2015 Ebola outbreak, which nearly doubled survival rates.
In addition, Regeneron is also evaluating the efficacy of the Monoclonal antibody (mAb) Sarilumab (also known as Kevzara) for treating severe COVID-19 cases. This protein-based therapy drug is known for treating moderate to severe Rheumatoid Arthritis (RA). It binds to membrane bound and soluble interleukin 6 (IL-6) receptor forms. More on the drug here.
Source (all of above information):
StatNews. "An updated guide to the coronavirus drugs and vaccines in development," https://www.statnews.com/2020/03/19/an-updated-guide-to-the-coronavirus-drugs-and-vaccines-in-development/
Regeneron Pharmaceuticals. "REGENERON’S COVID-19 RESPONSE EFFORTS," https://www.regeneron.com/covid19
Regeneron Pharmaceuticals. "REGENERON ANNOUNCES IMPORTANT ADVANCES IN NOVEL COVID-19 ANTIBODY PROGRAM," https://investor.regeneron.com/news-releases/news-release-details/regeneron-announces-important-advances-novel-covid-19-antibody
DrugBank. "Sarilumab," https://www.drugbank.ca/drugs/DB11767
Above is the protein structure of Sarilumab
CHEMICAL FORMULA: C6388H9918N1718O1998S44
DrugBank, https://www.drugbank.ca/drugs/DB11767
VirBiotechnology, a Biotech company headquartered in San Francisco, CA, is focused on infectious diseases. It has isolated antibodies from SARS-CoV survivors to see if they will be effective in treating the novel Coronavirus, which is homologous to SARS-CoV. Unlike Regeneron Pharmaceuticals, Vir Biotechnology is modifying one antibody to last longer in the body and induce long-term immunity by spurring the production of white blood cells, playing the role of a treatment and a vaccine. The company says that their neutralizing antibody binds to the highly conserved epitope of SARS-CoV-2, SARS-CoV. More here.
Sources (all of above information):
StatNews. "An updated guide to the coronavirus drugs and vaccines in development," https://www.statnews.com/2020/03/19/an-updated-guide-to-the-coronavirus-drugs-and-vaccines-in-development/
StatNews. "Vir Biotechnology reports early progress in antibody treatment for Covid-19," https://www.statnews.com/2020/03/25/vir-biotechnology-reports-early-progress-in-antibody-treatment-for-covid-19/
FierceBiotech. "Scangos' Vir Biotechnology to test COVID-19 antibody 'in the summer'," https://www.fiercebiotech.com/biotech/scangos-vir-biotechnology-to-test-covid-19-antibody-summer
Polyclonal Hyperimmune Immunoglobulin Medicine TAK-888 (Plasma-derived therapy): Takeda Pharmaceuticals
Polyclonal Hyperimmune Immunoglobulin Medicine TAK-888 (Plasma-derived therapy): Takeda Pharmaceuticals
The Japanese company, Takeda Pharmaceuticals, is isolating protective antibodies from the blood of COVID-19 survivors. They hope that the protective antibodies that kept these patients alive can be used to treat other COVID-19 patients. Currently, Takeda is investigating the development of an unbranded anti-SARS-CoV-2 polyclonal hyperimmune immunoglobulin medicine as a potential treatment against the virus. According to ScienceDirect, Hyperimmune immunoglobin is prepared from the plasma of donors who have many potent antibodies against an antigen. This process of deriving protective antibodies from human blood was used even during the Spanish Flu pandemic of 1918.
Sources (all of above information):
StatNews. "An updated guide to the coronavirus drugs and vaccines in development," https://www.statnews.com/2020/03/19/an-updated-guide-to-the-coronavirus-drugs-and-vaccines-in-development/
Takeda. "Global Plasma Leaders Collaborate to Accelerate Development of Potential COVID-19 Hyperimmune Therapy," https://www.takeda.com/newsroom/newsreleases/2020/global-plasma-leaders-collaborate-to-accelerate-development-of-potential-covid-19-hyperimmune-therapy/
From NCBI, https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4721910/
The Chinese drug company Ascletis Pharma, based in Hangzhou, China, proposed the possibility of combining Danoprevir, an antiviral drug for treating hepatitis C, and Ritonavir, an antiviral drug for treating HIV, to treat the Coronavirus disease. Both drugs are protease inhibitors.
Sources (all of above information):
StatNews. "An updated guide to the coronavirus drugs and vaccines in development," https://www.statnews.com/2020/03/19/an-updated-guide-to-the-coronavirus-drugs-and-vaccines-in-development/
Danoprevir chemical structure
Danoprevir chemical structure
Image Credit: Wikipedia, https://en.wikipedia.org/wiki/Danoprevir
Ritonavir chemical structure
Ritonavir chemical structure
Image Credit: Wikipedia, https://en.wikipedia.org/wiki/Ritonavir
AbbVie, an American biopharmaceutical company headquartered in North Chicago, IL, is testing the antiviral cocktail lopinavir/ritonavir as a potential COVID-19 treatment. At the start of the COVID-19 outbreak, hospitalized patients in China were given α-interferon combined with the repurposed drug Kaletra. Kaletra is an approved cocktail of the HIV protease inhibitors lopinavir and ritonavir and is used for treating HIV infections. Now, the repurposed kaletra is being combined with other drugs like ribavirin (antiviral guanosine analog), emtricitabine/tenofovir alafenamide fumarate (nucleoside reverse transcriptase inhibitor), baloxavir marboxil (influenza drug), and umifenovir (antiviral host-targeting agent). The World Health Organization (WHO) recommends that combining the repurposed drug kaletra with other antivirals would be effective in treating COVID-19. However, clinical trials with kaletra will only begin at the end of May.
The 3-chymotrypsin-like protease and the papain-like protease are the two main proteases in SARS-CoV, which are involved in Protelytic cleavage of the S-protein. Kaletra is thought to inhibit the 3-chymotrypsin-like protease in SARS-CoV and MERS-CoV. In fact, it improved clinical trial outcomes during the SARS-CoV outbreak and rapidly improved the health of a COVID-19 patient (reported by Ascletis Pharma in China). Studies done at the molecular level show that "flap closing" occurs when Lopinavir binds to the CL-like protease in SARS-CoV.
Sources (all of above information):
Sarma P, Prajapat M, Avti P, Kaur H, Kumar S, Medhi B. Therapeutic options for the treatment of 2019-novel coronavirus: An evidence-based approach. Indian J Pharmacol [serial online] 2020 [cited 2020 Apr 6];52:1-5. Available from: http://www.ijp-online.com/text.asp?2020/52/1/1/280269
Nature Biotechnology. "Coronavirus puts drug repurposing on the fast track," https://www.nature.com/articles/d41587-020-00003-1
Image Credit: PDB, https://www.rcsb.org/structure/4NJV
Image Credit: PDB, https://www.rcsb.org/structure/1MUI
Below are more drug and cocktail combinations as of February 15th 2020
Below are more drug and cocktail combinations as of February 15th 2020
Source: Nature Biotechnology. "Coronavirus puts drug repurposing on the fast track," https://www.nature.com/articles/d41587-020-00003-1
Source: Nature Biotechnology. "Coronavirus puts drug repurposing on the fast track," https://www.nature.com/articles/d41587-020-00003-1
SOURCES TO USE:
file:///C:/Users/Aparna/Downloads/preprints202002.0242.v1.pdf
https://www.sciencedaily.com/releases/2020/04/200402144508.htm
https://www.biopharmadive.com/news/coronavirus-inovio-vaccine-first-dose-human/575607/
https://www.raps.org/news-and-articles/news-articles/2020/3/covid-19-vaccine-tracker
Get Updated on New Approaches Being Tested in Clinical Trials to Treat COVID-19
Get Updated on New Approaches Being Tested in Clinical Trials to Treat COVID-19
Source: NIH: U.S. National Library of Medicine, https://clinicaltrials.gov/ct2/results?cond=COVID-19
Source: NIH: U.S. National Library of Medicine, https://clinicaltrials.gov/ct2/results?cond=COVID-19
The company Eli Lilly, also partnered with the Canadian firm AbCellera is working to find the most effective antibodies that fight against SARS-CoV-2. By taking a blood sample from a COVID-19 survivor, AbCellera identified more than 500 antibodies that might effectively fight the Coronavirus. Both companies now want to find the most potent antibodies from this blood sample in order to develop a treatment for COVID-19.
Source (all of above information):
StatNews. "An updated guide to the coronavirus drugs and vaccines in development," https://www.statnews.com/2020/03/19/an-updated-guide-to-the-coronavirus-drugs-and-vaccines-in-development/
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