Posted on : April 23, 2020 by Clinic One on Blog
How does a vaccine work?
First, we have to understand how our body works when a foreign organism (bacteria, viruses) enter our body. Our immune system, which helps us to deactivate and kill foreign organisms, has an essential role in it. Our immune system produces antibodies (proteins) that combat these intruders. The antibody also remembers viruses or bacteria that it has already come across. This is called immunity against a disease.
The purpose of a vaccine is to intentionally expose our body to viruses or bacteria which evokes an immune response and remember it for the future. The component of a vaccine could be the killed or weakened form of the virus. The vaccine can also contain unique viral proteins or molecules that are present on the surface of the virus. These are known as antigens, which help to start an immune response in our body. In immunology, an antigen is a foreign element that induces the production of antibodies in humans.
As simple as it sounds, the production of a vaccine is a very complex and regulated process. There are many phases in the large scale development of a vaccine. Generally, the phases include the exploratory stage, pre-clinical stage, phase I, II and III vaccine trials, approval, and licensing. The monitor and regulation of the vaccine continue even after it is released into the market. The exploratory stage is where the scientists study the virus and determine the best component of the virus, which would elicit an immune response. In other words, what should be the antigen for the vaccine?
Viruses are host specific and only reproduce in their preferred cells. The pre-clinical stage is the phase where the kind of cell lines (to grow the virus) is studied. Suitable animal models (monkey, ferret, mice) for the injection and study of the candidate vaccine are also studied. This is the stage where many vaccine developments get stalled.
Generally, the right antigen (virus component) for the vaccine, the optimal cell line, and the right animal model to test the vaccine, is difficult to optimize. Phase I, II, and III vaccine trials involve the assessment of the virus in humans. Phase I only uses a small group of people to test the initial efficiency of the vaccine. Phase II tests the vaccine in a larger group of people (a few hundred) which also contains people who are at risk of getting the disease. And Phase III trial tests the candidate vaccine in thousands of people.
One of the potential dangers of viral vaccine is that it sometimes shows what is known as a paradoxical phenomenon. This was evident in the case of SARS-CoV-1 (originated in 2002), where model animals/patients developed severe reactions when they got exposed to the virus, even after they were vaccinated. There are no effective vaccines for SARS-CoV-1 and MERS (Middle East Respiratory Syndrome) coronavirus.
What are the recent technologies and approaches at our disposal for the COVID-19 candidate vaccine?
The Coalition of Epidemic Preparedness Innovations (CEPI) has pledged US$ 2 billion to develop a vaccine candidate. As of April 2020, 79 projects from companies and academic institutes are underway to find a vaccine. According to CEPI, out of the 79 projects, 74 are in the exploratory or pre-clinical stage of production. Understanding the anatomy of the SARS-CoV-2 (a coronavirus that causes COVID-19) is essential during the exploratory stage of vaccine production. SARS-CoV-2 is an RNA virus, and which is prone to mutation.
SARS-CoV-2 has a protein known as Spike protein, which is present in the outer layer of the viral particle. This Spike protein is an antigen candidate that could be used as a prime element in the vaccine.
A modern approach such as nucleic acid vaccine has also gained attraction. One of which is known as a DNA vaccine. Before understanding the DNA vaccine, we have to know what is known as the central dogma of molecular biology. In a cell, DNA is transcribed into mRNA (messenger RNA), which is further translated into a protein. So, DNA has all the information on which protein is to be produced.
DNA vaccine uses the introduction of a short sequence of DNA into humans with the help of weakened viruses (not harmful), which make viral protein (e.g. Spike protein). In theory, DNA vaccine has the genetic material to make a viral protein inside human cells that could act as an antigen. Once the viral protein is made, the host body will make antibodies against it. DNA vaccines have never been tested in humans, so it may turn out to be a fresh candidate.
Another vaccine technology uses the mRNA (messenger RNA) vaccine which performs the same role as a DNA vaccine. The RNA vaccine skips the DNA part, by dosing the human cells with only the mRNA, which further codes for a viral protein (antigen). Remember, mRNA is the messenger between DNA and protein.
These mRNA and DNA vaccines technology are at the core of vaccine production for SARS-CoV-19.
Moderna, a Massachusetts based biotechnology company has developed an mRNA vaccine candidate named mRNA-1273, which is in phase I clinical trial for humans. This mRNA makes/codes the Spike protein of the SARS-CoV-2. The first human trial was done on 16th March 2020 and phases II will likely begin in the second quarter of 2020.
INOVIO Pharmaceuticals with International Vaccine Institute (IVI) has developed a DNA vaccine candidate which is known as INO-4800. They first started phase I trial in the US on 6th April 2020 with 40 healthy volunteers. INOVIO was also involved in the trial of a DNA vaccine that was targeted against MERS (Middle East Respiratory Syndrome) virus.
The University of Oxford, England has also created a COVID-19 candidate vaccine known as ChAdOx1 nCoV-19. This technology involves the use of an adenovirus, which is a common virus. They use a weakened adenovirus that has been genetically engineered to produce the Spike protein of the coronavirus. Once vaccinated, the adenovirus enters a human cell and produces the Spike protein which will initiate an immune response. The clinical trial for this vaccine started in March 2020 and is estimated to include 500 people.
CanSino Biologics (CanSinoBIO), a China-based company, has announced that its COVID-19 candidate vaccine Ad5-nCoV is entering the phase II trials in humans. They are preparing to use 500 volunteers for this stage. The phase I for Ad5-nCoV was carried out on 108 volunteers. This technology is based on CanSinoBIO’s adenovirus vaccine technique which has proved to be successful in developing an Ebola vaccine. The Ad5-nCoV vaccine also works by the production of SARS-CoV-2 Spike protein in humans, which would initiate an immune response.
Shenzhen Geno-Immune Medical Institute, based in China has also entered phase I of vaccine trial with a candidate vaccine named Covid-19/aAPC. The trial started in March with 100 volunteers. These are only a few of the candidate vaccine development that is going around the world.
The race to develop a vaccine against SARS-CoV-2 has already started. The final date for the large scale production of an effective vaccine is not certain now. One thing that stands between now and an effective vaccine is Time itself, but most of the researchers know that it is not going to be soon.
By Clinic One Team
April 23, 2020
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