The Various Covid-19 Vaccines

The Various Covid-19 Vaccines

Most vaccines have been in use for decades, with millions of people receiving them safely every year. As with all medicine, every vaccine must go through extensive and rigorous testing to ensure it is safe before it can be introduced in a country’s vaccine programme.
The goals of vaccine development are safety and efficacy. Safety here means that the vaccine should not have deadly side effects and not lead to any disease or infection. Covid-19 vaccines, too, have had to undergo different clinical phases before being made available in the market. The vaccines have to undergo pre-clinical and clinical trials and finally it needs to be approved by the medicine regulators of the country, in India by the Central Drugs Standard Control Organisation (CDSCO).
In pre-clinical trials, animals are monitored closely for any side effects like skin irritation, fatigue, fever or death. The serum of the animal is checked for antibodies. Then the animal is infected with SARS-coV2 virus. The animal is again monitored closely. If it survives without any adverse effects, the phase shifts from pre-clinical to clinical stage.
The clinical phase consists of three sub phases: 1, 2, and 3. These phases monitor toxicity and immunogenicity. The vaccine must be safe and effective in natural disease condition before being submitted for approval and general production.
In phase 1, the vaccine is given to a small number of people. Vaccine is generally given to normal healthy subjects. The primary observation is for detection of any side effects. The vaccine dosage has an upper and a lower limit. Upper limit means that if vaccine is administered in more quantity, the chances of developing side effects are more. Lower limit means if the vaccine is administered in small quantity, the chances of immune response or antibody production are also less. So, it’s important to administer appropriate dosage.
In phase 2, the vaccine is again administered to humans but the number of participants is higher, between 100 and 1,000. In this phase participants can be of different sex, race, colour, and they can be healthy or sick. All the participants are monitored closely for any side effects. The appropriate dosage is determined.
In phase 3, the number of participants is more, from 1,000 to 10,000. For AstraZeneca vaccine trial, it was 1,000-60,000.
When the vaccine passes the three phases successfully, it’s then sent for approval. In the USA, the Food and Drug Administration (FDA) is responsible for approving vaccines. On December 11, 2020, the FDA gave emergency use approval (EUA) for Pfizer-BioNTech’s Covid-19 vaccine. On December 2, the UK’s Medicine and Healthcare and Products Regulatory Agency (MHRA) also gave approval to Pfizer-BioNTech’s vaccine.

Working of Vaccines
1. Moderna and Pfizer-BioNtech
This mRNA vaccine takes advantage of the process that cells use to make proteins, in order to trigger immune response and build immunity to SARS-coV2. These vaccines work on mRNA technology and use a rapid and simple production process.
The lipid nano particles encapsulate mRNA. Lipid nanoparticle is structurally a phospholipid bilayer which acts as a vector to transport mRNA to the host cell. When the vaccine is administered, the lipid nanoparticle fuses with the host cell and releases the mRNA into host cell. This mRNA uses the host cell’s ribosomes to make proteins. This process is called translation.
SARS-coV2 has spikes made up of S-protein. The protein which ribosomes make in the host cell is the same as S-protein which is found on the virus. This S-protein gets attached outside the cell on MHC-II. MHC helps in interaction with other immune system cells. MHC-II is present on Antigen Presenting Cells (APC). MHC-I is present on all the cells of the body. MHC-II will bind to TCR (T-Cell Receptor) of helper T-Cell. Due to this, T-helper cell will get activated and start releasing Cytokines (IL1, 2, 3, 4). These Cytokines help B-cells to proliferate and differentiate and release antibodies. These antibodies are against the S-protein of SARS-coV2. Now, the S-protein which was produced gets attached to MHC-I. MCH-I binds to CD4 receptor of T-cytotoxic cell and destroys the cell containing S-protein by releasing destructive enzymes. This happens when SARS-coV2 infects cells.

2. Astrazeneca/ Oxford vaccine
It is not an mRNA vaccine. It uses a vector called chimpanzee adenovirus. Chimpanzee adenovirus contains DNA as a genetic material. When chimpanzee adenovirus is administered into humans, it doesn’t generate immune response but gets attached to the cell and releases DNA. This DNA migrates to host cell nucleus but is not incorporated with the host cell DNA. This DNA uses host cell enzymes and gets converted to mRNA, the process called transcription.
This mRNA uses host cell ribosomes to form protein. This protein is same as S-protein found on SARS-coV2. This protein will get attached to MHC-I and MHC-II and will initiate immune response, as already explained.

Vaccine efficacy
Vaccine efficacy is the percentage reduction in a disease in a group of people who received the vaccine in clinical trials. The higher the value of vaccine efficacy, the better the performance of the potential vaccine.
Moderna’s vaccine trials involved 30,000 participants. Half of them received the vaccine and the remaining “Placebo” received saline, that is, they did not receive the vaccine.
The vaccine was given to half of the participants on day 1 and then again on day 28. After 14 days it was checked whether a person developed symptoms of Covid-19 or not.
In the placebo group, 185 tested positive for Covid-19, while among those who received vaccine, only 11 people tested positive.
In placebo there were 30 severe cases, while there was no severe case in vaccinated participants.
Moderna’s vaccine showed 94.1% efficacy at preventing Covid-19.
The Pfizer/BIoNTech vaccine trial involved 40,000 participants. Again, half of them received the vaccine and remaining “placebo” received saline.
The participants received vaccine on day 1 and day 21. After 7 days it was checked whether symptoms had developed or not. In the placebo group, 162 tested positive, while 8 tested positive among those who received the vaccine.
Pfizer/ BioNTech showed efficacy of 95% against SARS-coV2.
The Astrazeneca vaccine trial involved total 12,000 participants. Out of 12000, 9,000 were present in Brazil and 3,000 in the UK. Half of them, the ‘placebo’ group, received saline and the other half received the vaccine. In Brazil, full dose of the vaccine was given on day 1 and again on day 28. In the UK on day 1, 1/2 dose was given and on day 28 full dose was given. Efficacy in Brazil was 62%, while in UK it was 90%. Total efficacy was 70%.
Among participants who tested positive, none of them had severe symptoms
Why 1/2 dose had efficacy of 90% and full dose had 62% is still unknown.

The writer is an MBBS student. qadeermir07@gmail.com

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