Decision to reduce time gap for precautionary dose based on economic considerations, not science: Virologists

Virologists have termed the Union Heath Ministry’s decision to reduce the mandated time interval between the second dose of COVID vaccine and the third ‘precautionary dose’ from nine months to six as ad hoc, asserting that it seems to have been guided by economic considerations rather than scientific ones.

Pointing out that the Union government and National Technical Advisory Group on Immunisation (NTAGI) had chosen to call the third vaccine shot as a ‘precautionary dose’ rather than a booster dose, NTAGI member Dr Jaiprakash Muliyil said there was no science behind the decision to reduce the time interval.

“It’s economics. We have a lot of manufactured vaccines waiting to be sold, but the current vaccines work against the first few Coronavirus variants - Alpha, Beta, Delta and Gamma. The Omicron has all but wiped out the previous Covid-19 strains and is also evolving and mutating quickly,” said Muliyil.

Dr Vineeta Bal, scientist at National Institute of Immunology, said no data-based clinical trial had been held for Indian vaccines to determine whether a precautionary dose was better after a time gap of six months or nine. “So, we are going by history of virology. We know that a two-dose regimen will result in immunity and the infection will slowly go down,” she added.

The government probably decided to ask people to go in the third dose earlier because a new variant is around, she quipped.

It was reported earlier this week by an Israeli expert that a new sub-variant of Omicron BA.2.75, which may be "alarming" in nature, had been detected in about 10 states in the country. However, the Health Ministry is yet to confirm the presence of these variants in the country.

According to Indian SARS-CoV-2 Genomics Consortium (INSACOG), the first confirmed case of the BA.4 Omicron variant in India was reported from Hyderabad in May this year.

There are different sub-lineages of the Omicron variant — BA.1, BA.2, BA.3, B.4, BA.5, BA.1.1 — but BA.2 is the dominant variant globally due to higher transmissibility.

Weighing in on the controversy, Dr Anurag Agrawal, dean of Biosciences and Health Research at Ashoka University, remarked that the government’s decision to reduce the recommended time interval seemed to be partly ad-hoc, driven by the principal consideration of adequately protecting those who were particularly vulnerable, such as the elderly, by administering the precautionary dose.

“There is no precise bioscience to it since there simply isn’t enough local data. Since our vaccines are not being used in the countries that generate the most data, we cannot substitute this with global data. Understandably, such decisions are based on logistics and economics as well as biomedicine. In itself that is not wrong, but better communication would be helpful,” said Agrawal, former director of Institute of Genomics and Integrative Biology.

He noted that most information available based on foreign data is for protein sub-unit vaccines and sufficient data was not available in India to advocate for any changes in the vaccine policy.

Several virologists including Muliyil questioned the efficacy of similar vaccines in countering newer strains.

“This third dose is called a precautionary dose. And it was initially for the elderly and those with co-morbidities. The picture changed after the Omicron wave hit us. Omicron is fairly immunogenic, but it keeps evolving quite fast. We have to remember that Omicron infects you even if previously vaccinated or infected,” Muliyil said.

He maintained that the current vaccines worked well against the Delta variant, which is no longer present, but people believe that it may help counter the Omicron variant as well.

Homologous boosters vs Heterologous boosters

Dr Shahid Jameel, virologist and fellow, Green Templeton College, University of Oxford, observed that as per science, the later the booster was injected, the better was the immune memory consolidation.

“But in a pandemic situation, it’s always going to be a trade-off for risk versus benefit. Reducing the gap to six months is sensible because you want to protect the vulnerable as soon as possible and still use vaccines prudently to develop good immune memory,” he said.

However, Jameel underscored that it also depends on what vaccine is being used for the two primary doses.

The COV-BOOST trial done in the UK addressed this question. Data showed that mRNA vaccines are boosted best with the same. However, if the primary doses are of AstraZeneca vaccine (called Covishield in India), then the best boosting is with a mRNA vaccine and the next best with the Novavax protein vaccine (Covovax in India).

When you use use the same type of vaccine as the first and second doses, they are known as homologous boosters and if you use a different vaccine platform from the first couple of doses, they are known as heterologous boosters.

A study in The Lancet had stated that heterologous boosters increased neutralising antibody titers by a factor of 6 to 73, while homologous boosters increased it only by a factor of 4 to 20. Antibody titers are specialised antibodies that bind pathogens and prevent them from spreading infection.

A study published in The BMJ pointed out that heterologous boosting using two dose adenovirus vector vaccines with one mRNA vaccine has a satisfactory vaccine effectiveness of 88%, but a three dose mRNA regimen was found to be the most effective against asymptomatic and symptomatic Covid-19 infections.

Recent vaccine data from CMC Vellore in Tamil Nadu showed that two doses of Covaxin and a boost with Covaxin gave a six-fold increase in antibodies starting from a low baseline. Two doses of Covishield and a boost with Covishield gave a 6.8X increase in antibodies starting from a high baseline.

However, two doses of Covishield and a boost with Covaxin gave only 2.5X increase in antibodies. But, two doses of Covaxin and a boost with Covishield gave 58X increase in antibodies.

“Since India has given mainly Covishield and Covaxin, it is best to boost people who got Covaxin with Covishield, and those who got Covishield with the same. It would be even better to boost Covishield recipients with Covovax, which is licensed in India and exported by Serum Institute of India,” observed Jameel, who since December 2021 has been advocating that the Centre needed to formulate a booster dose policy as he was of the opinion that Covishield or Covaxin may not be effective as the third dose.

Agrawal pointed out that the best available booster vaccine type, based on foreign data, is protein sub-unit vaccines. “However, to advocate for any major changes in the vaccine policy, we do need local data, especially now when most Indians already have hybrid immunity,” he said.

India has a large population that suffers from diabetes, cancer and cardiovascular disease, pointed out Jameel, and all of them would benefit from boosters as it raises the antibody levels and consolidates immune memory. “The higher number of antibodies protect better against infection in the short term, while immune memory protects against severe disease in the longer term. Antibodies wane with time and the new variants also escape them better,” he said.

Though most virologists advocate for an mRNA vaccine as the third shot, Agrawal notes that there’s not much data available on the country’s first homegrown Covid-19 vaccine Gemcovac, developed by Pune-based Gennova Biopharmaceuticals. The Drug Controller General of India (DGCI) approved the two-dose mRNA vaccine for emergency use for the age group 18 and above in the last week of June.

“The new mRNA vaccine Gennovac may be very useful as a rapidly adaptable booster suited for our cold chain. I hope to see more data on it in the coming time,” added Agrawal.

Muliyil said that we are currently in an endemic state as the virus is changing rapidly and there are currently no guidelines as to what to do.