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Booster Doses in India: Key Questions That Remain to be Answered

Dr Satyajit Rath says all conversation about booster doses in India is based on "sketchy evidence" as yet.

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Booster Doses in India: Key Questions That Remain to be Answered
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With the National Technical Advisory Group on Immunisation (NTAGI) meeting to decide India's COVID-19 booster dose policy, there has been a trickle of information coming in on differences between experts on if India needs boosters and if yes, which ones. The broad consensus, as reported by The Indian Express, is that while we need a booster dose, boosters of Covishield and Covaxin will not work. A booster dose from a different platform is what is needed to see real results.

But what platforms should these be? Will a booster of Covishield over two primary doses of the same platform work? What about Covaxin? And finally what data do we have on boosters in India, to really start rolling out the shots.

FIT spoke with Dr Satyajit Rath, an immunologist with National Institute of Immunology, virologist Dr Shahid Jameel, fellow, OCIS at Green Templeton College at Oxford University, and Dr Rakesh Mishra, former director of CSIR-Centre for Cellular and Molecular Biology, to answer some of these questions.

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Can a Booster of Covishield Work? 

Nearly 90 percent of India's COVID-19 vaccination programme has been driven by Covishield, manufactured in India by Serum Institute of India. Covishield continues to be the primary vaccine being used in India despite several new vaccines receiving emergency approvals, including - Covaxin, Zydus Cadila, Johnson & Johnson, Sputnik V.

Covishield is a viral vector platform, developed by Oxford university and AstraZeneca.

The viral vector platform works by genetically modifying a weakened version of the adenovirus taken from chimpanzees. It is modified to contain genetic material shared by coronavirus. Once the vaccine is injected, it teaches the body's immune system to fight coronavirus.

Earlier in December, Serum Institute applied for permission to use its vaccine as a booster. The Subject Expert Committee (SEC) of the Central Drug Standard Control Organisation (CDSCO) asked SII to produce more data for the approval.

But will a Covishield booster work? Are there any studies to back this up?

In a previous interview with FIT, Dr Shahid Jameel, a leading virologist, said that Covishield cannot work as a booster and he hinted at limitations of the platform itself.

"Covishield is not a vaccine that you can use as a booster. If I have had two doses of Covishield, and I get a third dose of Covishield as a booster, it's not going to do very much to enhance my COVID immunity. And that's simply the way the vaccine is, the way the platform is."

"For booster doses for the HCWs or elderly immunocompromised, we need to look at importing mRNA vaccines," he added.

Most studies, including the latest study on Omicron virus, indicate that a booster of a different platform, more specifically the mRNA platform, will produce better results.

In the UK, while AstraZeneca has received approval for its use as a booster, something cited by SII to apply for booster doses in India, the programme there relies on Pfizer's vaccine or Moderna's half dose for its booster rollout.

In an interview with FIT, Dr Satyajit Rath says all conversation about booster doses in India is based on "sketchy evidence" as yet.

On Covishield he says, "Each subsequent dose of any vaccine will by and large trigger some increase in antibody levels." He adds,

"That said, there is some basis to think that repeat doses of adenoviral platform vaccines might generate somewhat lesser magnitudes of antibody levels against the specific vaccine target than a 'cross-over' dose of a different platform. But this is not because they won't 'work' as repeat doses, but because they will probably keep triggering responses against both the vector adenovirus and the specific COVID target."
Dr Satyajit Rath

On whether cross-platform boosters will produce better results, he says,

"Initial evidence so far indicates that a cross-platform repeat dose gives even higher increases in antibody levels. And since the studies of durations between repeat doses have not been particularly exhaustive or systematic as yet, any firm claims about what interval will 'work' are premature, I think."

Dr Rakesh Mishra points to a basic problem with the studies being done to test vaccine efficacy against Omicron. He says,

"In all the studies out so far, antibody neutralisation assay shows antibodies have decreased, but cell immunity is not being studied. That will take time and that immunity will be less compromised."

He talks about hybrid immunity - from previous infection and vaccine-induced immunity - giving Indians a unique advantage. All the sero-surveys have indicated high sero-positivity among Indians, specifically in urban pockets.

What About Covaxin? 

Dr Jameel says, "Covaxin third dose can be provided. The nature of the vaccine is that while it gives antibodies and helper T cells, it doesn't give what we call killer T cells. And that adds another layer of protection."

But lack of adequate data remains. Bharat Biotech, the makers of Covaxin received approval for its booster dose study six months after the primary 2 doses by the CDSCO in April. So far, no data seems to have been published or shared in public.

In August, Christian Medical College (CMC), Vellore, received approval to carry out India's first-ever clinical trials on a booster dose. This would include testing the efficacy of the third booster as well as mixing and matching vaccines for those who hadn't received any vaccines so far.

Virologist and member of the NTAGI, Dr Gagandeep Kang, in a recent twitter reach-out, indicated that Christian Medical College is enrolling participants for a Covaxin booster study. It is looking to enroll people who received Covaxin 3 to 6 months ago in Vellore, Chennai, Bengaluru and Delhi.

So What Platforms Should Work? 

Dr Jameel in the earlier interview pointed towards India's two protein-based vaccines.

"India also has two other protein-based vaccines. One is Novavax vaccine from Serum Institute, the other is a vaccine that Biological E has made, which are both protein vaccines which have gone through trials. The numbers look good, but they haven't been approved yet. So India may consider giving emergency approval to those protein vaccines to be used as boosters in healthcare workers."

Dr Rath says in the absence of any real data, any conversation around boosters is premature, but "any non-adenoviral platform vaccine might in fact work well after Covishield (such as Covaxin, or ZyCoV-D). Again, there are no really good data as yet, though."

"I don't think (and the SEC of the CDSCO apparently does too) that any vaccination protocols should be adopted without at least some evidence for them."
Dr Satyajit Rath
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So What Really Should India's Booster Programme Look Like? 

Dr Jameel says "India needs to make sure it is getting the vaccines to every eligible citizen as soon as possible, and perhaps should consider reducing the gap in Covishield to at least 12 weeks."

Dr Rath raises some critical questions on India's booster programme, saying perhaps India needs to first ensure every eligible person gets the primary two-dose vaccine. He says,

  • Maybe we should first try and get everyone vaccinated in our basic two-dose vaccination campaign, perhaps, before we plan a 'booster' programme?

  • Maybe we should worry about why SII says that they have no orders for Covishield from the government of India?

  • Maybe we should worry about why ZyCoV-D does not seem to be in actual use very much despite approval months ago, especially in below-18-year-olds for whom it is apparently approved (and no other vaccine is)?

Dr Mishra talks about the hope of getting vaccines for immunocompromised children before we roll out boosters for adults, "First of all, boosters will help. All you have to see is ROI - return on investment. Rolling out boosters is not wise at the cost of leaving a large number of people unvaccinated. Vaccines are also a social medicine.:

Dr Rath points to the desperate need to get vaccines to the countries that have been denied doses while the global north rolls out booster programmes for all:

"It seems to me that the ongoing COVID vaccination programme, both in India and the world, especially the global south, desperately needs more attention at the moment than 'boosters' do, particularly in the absence of clear, robust evidence as yet about the many practical issues about repeat doses."

(Subscribe to FIT on Telegram)

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