With two doses of vaccines proving to be less effective against the newly-detected Omicron variant of the coronavirus, many countries in Europe have stepped up their booster dose campaigns. Studies have shown that a third vaccine shot strengthens the body’s immune response against the virus significantly.

In India, health officials have so far publicly maintained that the country will first vaccinate its adult population with two doses of Covid-19 vaccines before introducing booster shots. About 42.4 crore people, or 44% of the country’s adult population, are still to be fully vaccinated, as of December 17.

Many, however, argue the country cannot afford to delay booster shots, at least for vulnerable groups like health workers and immunocompromised people.

Some, in fact, contend that there is no trade-off between vaccinating all adults and delivering booster shots to those already vaccinated because India has ample stocks of vaccines.

How robust is this claim? Does India indeed have enough vaccines to roll out booster shots to those already vaccinated, while also immunising its entire adult population?

The answer is complex, as Scroll.in found in an analysis based on available data on vaccine stockpiles as well as forecasts for vaccine supplies in the next two months.

India has so far vaccinated 56% of its adult population with two doses of Covid-19 vaccines. Photo: Arun Sankar/AFP

How the numbers stack up

Central government data for December 17 shows India has a stock of 166.6 million vaccine doses, which can be used to fully immunise another 8.3 crore people – approximately 8.6% of the country’s adult population.

This stockpile is not static – it grows as more vaccine supplies come in.

Scroll.in contacted both government officials and vaccine manufacturers for data on the vaccine supplies that India can tap in the near future. Officials of vaccine companies shared some numbers, on the condition of anonymity.

Serum Institute of India, the largest vaccine manufacturer in the country, which has contributed the bulk of vaccines used in India’s Covid-19 vaccination drive, can supply 500 million doses of Covishield in the next two months, a company official said. Of these, about half the doses, or 250 million, are ready, and the other half can be manufactured soon, provided the government places an order. The government is yet to place fresh orders with the company, CEO Adar Poonawalla said in an interview with CNBC-TV18 on December 8.

Bharat Biotech, the supplier of Covaxin, can provide 55-60 million vaccine doses every month to the government, an official in the company said. Over two months, this comes to about 110-120 million doses.

Apart from these two vaccines, India has approved the emergency use of Sputnik V, ZyCov-D, Moderna, and Janssen vaccines. Both Moderna and Janssen vaccines are still locked in a dispute with the government over indemnity clauses – the manufacturers want protection from any legal action that may arise out of vaccine adverse events and the government is unwilling to concede that. A spokesperson for Johnson and Johnson, manufacturer of Janssen, said discussions with the government continue.

About 5.3 million Sputnik V doses have been administered in the country – just 0.3% of the total number of doses delivered. The Russian Direct Investment Fund, a wealth fund of the Russian government, which manages the Sputnik V vaccine, refused to comment on their current stockpile.

DNA-based ZyCoV-D, manufactured by Zydus Cadilla, received approval in August, but it is yet to be rolled out in the national immunisation programme for reasons that are unclear. The company did not respond to a query about its current stockpile. In August, managing director Dr Sharvil Patel had said the company can produce 30-40 million doses by December.

Assuming that these 40 million doses are available for use, and that the Indian government purchases all the stocks that Serum Institute and Bharat Biotech can supply in the next two months, the total stocks of three approved vaccines – Covishield, Covaxin, ZyCoV-D – would come to 660 million doses.

This would be enough to immunise 33 crore people. That still leaves about 10 crore adult Indians out of the vaccine net. If a part of these vaccine stocks are diverted towards booster shots, fewer doses would be available for the adult vaccination drive.

However, the picture changes dramatically, if we take into account other vaccines that are awaiting regulatory approval in India. The most promising among them are the protein-based Corbevax, produced by Biological E Ltd, and an mRNA vaccine made by Gennova Biopharmaceuticals, a subsidiary of Emcure Pharmaceuticals.

While Biological E Ltd has been submitting rolling data from the clinical trial of Corbevax to the drug regulator, Gennova is expected to complete the phase 2/3 trial of its vaccine by January 2022.

A senior government official, who did not want to be identified, said the Centre has placed an advance order for 300 million doses of Corbevax with Biological E Ltd. If the vaccine is approved, these doses “can be made available in the next 2-3 months”, the official said. When asked for a response, a spokesperson of Biological E declined comment and said the company was “awaiting approval from the government first”.

Gennova Biopharmaceuticals has committed 60 million doses of its mRNA vaccine to India, a member of the National Technical Advisory Group on Immunisation said.

Adding Corbevax and Gennova’s mRNA vaccine to the mix, India could have 960 million doses in the near future, which is enough to fully immunise its remaining adult population and still leave 100 million doses for booster shots.

However, there is a catch.

Most countries have adopted a heterologous booster vaccine policy – essentially, using a vaccine that is different from the first two doses as a booster shot. Some studies have shown this generates a better immune response.

If India adopts the same “mix-and-match” approach, the bulk of its vaccine stocks might not be suitable for booster shots.

About 88.7% of vaccine recipients in the country have been vaccinated with Covishield, a viral vector vaccine which inserts proteins of the virus into the body of a host to provoke an immune response. Covishield uses a chimpanzee adenovirus as a vector to carry the protein.

Virologist Dr Shahid Jameel, a senior research fellow at Oxford University, said those vaccinated with Covishield might not benefit much from a booster dose of the same vaccine “because the background vector immunity will not allow to raise the immunity against viral spike proteins”. Immunity against chimp proteins will grow, he said, but not against the spike proteins of the virus.

If India decides to deliver booster shots of a different vaccine, it currently has only Covaxin as an option. The production capacity of Bharat Biotech is limited to 55-60 million per month. India might find itself without enough vaccines for a full booster dose campaign in the near future, unless it approves new vaccines and rolls out ZyCoV-D that already has an emergency use authorisation since August.

A member of the National Technical Advisory Group on Immunisation, however, said that boosters, if approved, would be rolled out over a few months, which would provide enough time to stock more vaccines.

What studies show about booster shots

Omicron was labelled a “variant of concern” by the World Health Organisation on November 26. Samples collected from vaccinated and previously infected people in South Africa showed lower neutralisation activity – or reduced ability of antibodies to defend a person against the virus – in the case of Omicron as compared to other variants.

The WHO noted that Omicron is able to evade the body’s immune response because it has more than 30 mutations in the spike proteins that bind the virus to the host cell.

Studies from Israel and the United Kingdom have shown boosters are able to reinforce immunity against the virus. The Israeli study, published in the New England Journal of Medicine, found that senior citizens administered booster doses had 19.5 times less chances of contracting severe illness than those who had not received a booster dose.

Over 70 countries have already opted for booster doses, data from Our World In Data shows.

In most of these countries, the booster dose is of a different vaccine than the one used for the primary vaccination. For instance, Israel is administering Pfizer-BioNTech as a booster, irrespective of the first and second dose.

The UK government initially recommended Pfizer-BioNTech for boosters, but subsequently introduced Moderna, keeping AstraZeneca boosters limited to those who have received only one of two doses of the vaccine. This decision is based on the Cov-Boost trial that studied 2,878 people who were randomly administered one of seven vaccines as a booster, if their primary vaccination was Astrazeneca or Pfizer-BioNTech. In its latest guideline, the UK government said booster doses of Moderna and Pfizer produce substantial antibodies.

The United Kingdom began its booster dose drive with the Pfizer-BioNtech vaccine. Photo: Paul Ellis/AFP

So far, studies done to assess efficacy of heterologous combinations of vaccines have been largely limited to mRNA vaccine platforms such as Moderna and Pfizer-BioNtech. Both these vaccines are not being administered in India.

Of the vaccines administered in India, Sputnik and Covishield, the Indian version of AstraZeneca, are viral vector vaccines, while Covaxin is a whole inactivated virus vaccine.

Dr Gagandeep Kang, microbiologist and virologist from the Christian Medical College, Vellore, said no large-scale study has been conducted in India to assess the immune response produced by a booster shot of Covaxin in a person vaccinated with Covishield and vice-versa. The Christian Medical College is currently inviting participants for a multi-centre study that started in September in which those fully vaccinated with either Covishield or Covaxin are being given a booster dose of the other vaccine.

“The study has suddenly become urgent in light of the Omicron variant,” Kang said. The researchers are aiming to complete it by the end of January 2022.

Kang, however, pointed out that there is no data yet to suggest that Covishield cannot be used as a booster after it has been used for primary vaccination. “Which means, if India wants, it can use Covishield as boosters even for those who received the first and second doses of Covishield,” she said. Australia, for instance, uses Astrazeneca as a booster for people immunised with the vaccine, if Pfizer is not available for a booster shot.

She added, “But ideally, India must first focus on immunising everyone with both doses, then give additional shots doses to immunocompromised people and then think of boosters.”

Experts who are part of the National Technical Advisory Group on Immunisation say they are awaiting preliminary evidence on breakthrough infection in the Indian population before they take a decision on boosters. Breakthrough infection refers to cases where a fully vaccinated person still ends up getting infected with the virus.

Scientists at the National Institute of Virology “are growing the virus to check whether vaccines used in India are effective against the Omicron variant,” said Dr NK Arora, member of the National Technical Advisory Group on Immunisation.

Arora said since the immune profile of Indians is different from populations that have been studied as part of the research on booster doses, it was important to gauge vaccine efficacy in the Indian population before finalising the country’s booster policy.

This reporting was supported by a grant from the Thakur Family Foundation. Thakur Family Foundation has not exercised any editorial control over the contents of this article.