Sooner or later, India has to develop Omicron-based boosters

Vaccines based on Omicron variants are better than the ones based on the ancestral strain, but the older vaccines are still effective

Updated - January 01, 2023 12:42 am IST

Published - December 31, 2022 08:30 pm IST

A health worker prepares a dose of a COVID-19 vaccine at a primary health centre in Chennai’s Virugambakkam on December 28, 2022.

A health worker prepares a dose of a COVID-19 vaccine at a primary health centre in Chennai’s Virugambakkam on December 28, 2022. | Photo Credit: The Hindu

Three years after the SARS-CoV-2 outbreak in Wuhan, China is witnessing a very high number of daily fresh infections after abruptly abandoning the zero-COVID strategy, leading to hospitals getting overwhelmed and crematoriums struggling to cope up with a large influx of bodies. In response, countries across the world, India included, have taken several measures to keep the virus spread from China under check. 

The exponential increase in daily infections — an estimated 250 million people infected in just 20 days in December — and a high number of deaths in China have brought the focus back to booster shots. Though a few dozen genome sequences shared by Chinese researchers do not indicate the emergence of any new variants, the high infection rate can possibly churn out new variants with even greater transmissibility, and possibly greater disease severity. Like primary vaccination, should administering a booster shot to all adults in India be necessary? 

With nearly 92% of adults in India fully vaccinated by mid-October and a very large percentage of people also naturally infected, the hybrid immunity among adults in India is very high. But the uptake of a booster dose by adults over 18 years has been low — just 28% of adults have taken a booster dose as of December 21. Besides high hybrid immunity in the population, the other reason for the low uptake could be due to Omicron sub-lineages causing only a mild disease without high rates of hospitalisations and deaths. If making the booster shots free only for adults over 60 years might have increased the hesitancy, the uptake did not increase much even when made free for all adults for 75 days beginning mid-July.

Not for all adults

“Personally, I do not believe that booster doses are needed for healthy adults at this time as a public health tool. The bulk of the country has hybrid immunity. The risk of severe disease and hospitalisations is low in generally healthy individuals,” Dr. Gagandeep Kang, Professor of Microbiology at CMC Vellore, says in an email to The Hindu

Dr. Chandrakant Lahariya, physician epidemiologist, concurs with Dr. Kang. “In an Indian setting with high hybrid immunity, the benefit of a third shot is very marginal for healthy adults, if any,” he says in an email. “The vulnerable population sub-groups (over 60 years and those with co-morbidities in the 18-59 years age-group) should get a third dose irrespective of the history of a confirmed COVID-19 infection.” 

Dr. Lahariya adds, “The need for a booster is influenced by multiple determinants including vaccine used, vaccine dose interval, whether vaccine was administered before or after natural infection. Currently, for settings such as India, there is not enough evidence to use boosters for all adults.”

Data from other countries indicate that a booster dose may provide marginal benefit only for a small period of time. “This seems to hold for risk groups and non-risk groups, with greater benefit for those at higher risk. There is a caveat that the data from other countries are from very different population structures and with the use of vaccines that are different from those used in India,” says Dr. Kang. 

The bigger concern in India is the non-availability of data on the effectiveness of vaccination with two doses to make well-informed decisions about booster doses in adults.

“There are no data from India that show that any risk or age group has waning effectiveness of vaccines. The booster dose was rolled out in India about a year ago, labelled as a precautionary dose because there was no data demonstrating waning efficacy [of primary vaccination]. That situation still holds, we have no data,” she says. “We can infer that the vulnerable, like the rest of the country, may have been widely infected, but there is still some potential for benefit from a booster shot given that their immune responses are likely to be weaker, given the medical conditions that place them in vulnerable groups.” 

Still effective 

However, all vaccines currently approved and available in India have been developed based on the ancestral (Wuhan) strain. Though all Omicron sub-lineages and recombinant viruses show greater immune escape compared with the ancestral (Wuhan) strain, the vaccines available in India will still be effective as boosters against the Omicron subvariants. “Till now, evidence shows that vaccines based on the ancestral strain will continue to be effective with marginal reduction in clinical effectiveness against primary end points of moderate to severe disease caused by Omicron variants,” says Dr. Lahariya.

“Data [from other countries] indicates that vaccines that are based on the ancestral strain can be effective boosters against Omicron. Vaccines that are developed based on the Omicron strain are somewhat better than the ones based on the ancestral strain, but it isn’t as if the vaccines based on the ancestral strain do not work at all,” she says.

Just like there is no clinical effectiveness data of full vaccination, no studies have been done in India to understand the effectiveness of boosters either. “As far as I am aware, there are no clinical effectiveness studies of boosters against the Omicron variants in India. A few studies have looked at neutralising or surrogate neutralising antibodies to Omicron, but there is no data to show where the boosters actually prevent disease,” Dr. Kang says. 

Omicron boosters

Pfizer and Moderna have developed and made available bivalent booster shots. In contrast to vaccines used as a booster shot in India, bivalent boosters have half of the mRNA coding for the spike protein of the ancestral virus strain and the other half coding for the spike protein of the Omicron variant. Real-world data of Pfizer’s bivalent booster dose showed additional protection and more effectiveness in the older population than the original monovalent vaccine based on the ancestral strain. Pfizer has developed boosters using BA.4/BA.5 Omicron variants too. 

“If you look at the real-world data, the relevance of the data to India is limited — only a tiny proportion of the population that belongs to older age groups has been studied, and the actual number of cases of severe disease prevented was small. Nonetheless, there was some benefit and, therefore, we should think of developing booster doses based on currently circulating Omicron sub-lineages,” says Dr. Kang.

A large percentage of adults in India were infected by BA.1 and BA.2 sub-lineages of the Omicron during the third wave. Many more Omicron sub-lineages have emerged with even greater immune escape (and hence far higher transmissibility) during the past one year. How effective will Indian vaccines based on the ancestral strain be as a booster shot in the continuously evolving situation? 

“So far, vaccines developed against the Wuhan strain are still working for Omicron sub-lineages. As long as we do not have a variant that is very distant from previous variants, these vaccines should continue to work [as boosters],” Dr. Kang explains. “This creates a situation where we will see some initial benefit in India with boosting with vaccines now available. But as the virus evolves further, there will be less benefit when compared to boosters based on Omicron, either given singly or bivalent. Since these Omicron-based vaccines are not available in India, the vulnerable should be offered an additional dose of any vaccine.” 

Unlike when developing COVID-19 vaccines for primary vaccination in 2020, developing Omicron-specific vaccines for boosting need not have to go through all phases of a clinical trial. Given the high vaccination coverage and natural infection, it will not be possible to carry out phase-3 trials for efficacy. “Future approvals for new vaccines will be based on immunogenicity studies. Vaccines for SARS-CoV-2 are going to need to be considered by platform so that new versions can be easily developed,” she says. “But in order to know whether the vaccines are working or not, it is important to ensure that we have plans for vaccine effectiveness studies that will allow us to gather real-world evidence and make a call on whether to continue to use the vaccines or not.”

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