153 CMAAO CORONA FACTS and MYTH BUSTER ICMR Vaccine
Dr K Aggarwal
President CMAAO
With inputs from Dr Monica Vasudev
975: Round
Table Expert Zoom Meeting on “Covid-19 vaccine update”
17th July, 2020, 11am-12pm
Participants
Dr KK Aggarwal
Dr Ashok Gupta
Dr AK Agarwal
Dr Ashok Gupta
Dr Suneela Garg
Dr DR Rai
Dr Narottam Puri
Dr JA Jayalal
Dr Jayakrishnan AV
Dr Alex Thomas
Dr Atul M Kochhar
Dr Glory Alexander
Ms Meenakshi Datta Ghosh
Mrs Upasana Arora
Dr K Kalra
Ms Ira Gupta
Dr S Sharma
Faculty
Dr
NK Ganguly
Former Director-General, ICMR
Key
points from the discussion
- A herd immunity of 60-70% is required to stop the
spread of infection in the community; however, development of herd
immunity will take time. This can be achieved with vaccine.
- A vaccine which gives 40% protection may not be
ideal; if it gives 70% protection, it will stop transmission.
- In India, phase 1 and 2 trials only; phase 3 yet to
be done. Nineteen of the vaccines around the world have completed phase 1
or are in/completed phase 2 and have entered phase 3. Some international
vaccines have entered phase 3, so may come out with a vaccine earlier than
us.
- US FDA has brought out separate guidelines for
animal toxicology studies for Covid vaccine.
- Different platforms are being used to make the
vaccine safe. Very limited amount of the viral protein (such as preformed spike
protein, receptor binding domain [RBD]) is used to make it as safe as
possible. The whole cell vaccine (killed or attenuated) may cause problems
as they contain all viral antigens, which might produce immune responses.
- Immune responses in humans differ. This is why three
age groups will receive the vaccine: 18-55, 55-70, ≥70. Different
concentrations are taken and multiple injections are needed – one to prime
and the second to boost.
- Will the vaccine work will depend on whether
neutralizing antibodies are formed. They are checked in two formats: live
virus and ghost cells. Moderna vaccine (synthetic vaccine) was able to get
neutralizing antibodies in 8 of its subjects and it also passed safety
(there will be some swelling, redness at the site, fever, nausea but no
serious adverse effects like cytokine storm, autoimmune reaction). Moderna has finished phase 2, but
they have not published.
- Pfizer has taken four
different constructs of mRNA vaccine with BioNTech. Two of them have
completed phase 2.
- In India, Gennova
Pharmaceuticals is developing mRNA vaccine and have almost finished
preclinical studies. Their results in mice are good and in monkey
challenge are excellent. They have completed studies on plasma and did not
find any autoimmune reaction, cytokine storm or any deleterious immune
reaction.
- Till phase 3 is done, there is no certainty that the
vaccine will succeed. People may react differently according to the
endemicity like the Rota virus vaccine.
- No mRNA vaccine is in the market yet. Moderna and
Pfizer vaccines have gone into human trials; Gennova are almost completing
the animal and preclinical studies.
- Spike protein
vaccine (Astrazeneca and Oxford vaccine). They have given
license to several companies. In India, license has been given to Serum
Institute of India. If the vaccine succeeds in phase 2, they will start
manufacturing and release the vaccine as an emergency vaccine if phase 3
is successful.
- Novavax vaccine: Phase 2 is
completed. It is entering phase 3
trials in Australia and Brazil. Matrigel adjuvant is used. It is funded by
BARDA. Novavax has a joint venture with Cadila Pharma called CLP
Biologicals in Ahmedabad.
- There is a global list of 19 prospective companies;
no Indian company features on this list.
- The
Johnson & Johnson vaccine
is using Adeno-26 platform and pre-fusion spike protein, which has been
successfully used by them in Ebola vaccine (RNA vaccine) and RSV vaccine.
J&J has so far no agreement with any Indian company, but they are
talking to Aurobindo, which has bought a small vaccine company from Pfizer
in the US. It is using a vesicular stomatitis virus platform for vaccine
development, which is likely to be manufactured in their unit in
Hyderabad.
- Bharat Biotech
vaccine:
It is a whole cell killed vaccine.
There are few challenges: If it has an alum adjuvant, then it might
produce immune response. Since there are no human trials yet, we do not
know how it will behave.
- Sinovac
inactivated whole virus vaccine from China might be the first vaccine available.
It is alum adjuvanted and is already in human trials. Formaldehyde is used
to inactivate the virus.
- Most vaccine products are being tested in multiple
countries.
- In India, the regulatory pathway to monkey studies
is very long. For animal studies (monkey), one may have to go outside
India (Gennova). There are very few BSL 3 facilities to do animal
challenge studies.
- Many convalescent plasma have very little
neutralizing antibodies. Some of them have almost no antibodies. The
amount is not the same as it is produced in other infections.
- The amount of antibodies and the quality of
antibodies which the vaccine will produce will be very critical.
- NK cells are markers of innate immunity. If NK cells
are okay, then it is better.
- Mutations in the virus are happening rapidly now.
- Monoclonal therapy: One single antibody may not work
so a cocktail of three antibodies is preferred. Tocilizumab is actually
IL-6 inhibitor.
- Safety of the vaccine was a cause for concern
because of the nature of the virus right from Day 0. It attacks all organs
through immunological response (cytokine storm). This is why manufacturers
are trying to take as little as possible of the virus. Age difference is
critical; hence, three groups of populations are being studied in trials.
Like influenza vaccine, this vaccine may need to be taken every year.
- Cost of the vaccine will be a challenge.
