When the news of Omicron emerged from Africa at the end of November 2021, and the world was unsure what this rapidly spreading variant could do, we had the recommendation for a “precautionary” dose. Booster doses had begun to be rolled out across high-income countries, but primary two-dose coverage in low-income countries continued to lag.
In India, which had seen high death rates during April-May 2021, January 2022 brought many infections, many of which went untested and unreported. Although the precautionary dose was recommended, the Omicron wave was sharp and short, with an estimated 50–60% of the country infected within a few weeks. After that, we weathered the Omicron wave by mostly relying on two doses of vaccine with or without earlier infections. Although these did not protect us from infection with Omicron, they clearly protected us against severe disease and death.
The World Health Organisation recommended a booster dose with any available vaccine following its prioritisation framework of healthcare workers, the elderly, and those with comorbidities. This recommendation was based on data which showed that after about five months after vaccination with mRNA and adenovirus vectored vaccines, there was little protection against infection. However, there continued to be lower, but good, protection from severe disease and death.
Decisions on boosters are made based on whether vaccines are continuing to do what they are supposed to do, which is to protect the vaccinated from infection, disease or death in the real world. If vaccine-induced protection begins to decline, we can assess whether all people or some people, need to be given a booster and when. This needs a lot of data, and Israel, which turned its whole population into a living laboratory to show how mRNA vaccines worked, led the world in generating and using data.
Most countries which measured whether the vaccines worked in the real world used mRNA or adenovirus vectored vaccines, but data from Latin America showed that for primary immunisation, inactivated vaccines worked less effectively than adenovirus vectored vaccines. We now have data on boosters, mainly from high-income countries which used mRNA vaccines. There is also new data on bivalent boosters, which include the ancestral virus and Omicron, again from high-income countries, showing that in the elderly population, bivalent vaccines offer increased protection against severe disease and death.
In India, without data and vaccines different from the rest of the world, how do we decide on booster or ‘precautionary’ doses? The benefits of vaccination can be at two levels—the individual or the population.
For each individual, the goal is to protect against severe disease, and risks vary by age, other illnesses, and prior infections. For a generally healthy young person who has been vaccinated with two doses of vaccine and infected—as 90% of India has been, the risk of severe disease is low. Therefore, for a younger, healthier person, additional boosters are likely to have incremental benefits, not zero, but not huge.
However, for an older person, or one who is immunocompromised or has other illnesses, in general, the primary series of vaccines offers lower protection, and an additional dose may increase protection. Boosters will greatly benefit older individuals than younger people. However, for those older individuals with hybrid immunity from the previous infection, benefits from booster doses will be less.
Which vaccines should be used as boosters depends largely on what is available, but based on both immunogenicity data from India and effectiveness data from Latin America, those who have received inactivated vaccines should consider protein or adenovirus vectored vaccines. The latter is not widely used in younger populations or as boosters in high-income countries but has been used in Asia and Latin America. One of the worries with adenovirus vectored vaccines is a rare side effect which leads to small clots (called TTS or thrombosis with thrombocytopenia syndrome). This happens only with the first dose, so if it has not happened with the first two doses, it will not happen with a booster. But protein vaccines might be even safer than any other vaccine.
Data-driven timing and frequency of boosting is evolving, but in general, a booster dose can be taken, if needed, with a three-month gap after infection or vaccination. This does not mean that a booster should be taken every three months, but just that when a booster or third dose is needed, the gap should be at least three months. In some parts of the world, a fourth dose is being recommended, but there is no evidence of the amount of benefit such boosting might have, particularly in the context of India, which has had high infection rates.
From a policy point of view, does India need a booster for its entire population? At this time, no data from India indicates the need for a booster dose in any age or risk group. This may be a lack of data on how well vaccines are doing, but while we need to build the systems to get the data we need, we also need to consider what our public health needs are today and for the projected future. What other health issues do we need to tackle, and what is the relative importance of this infection? Is there enough Covid-19 in India today or projected into the future to make booster doses worthwhile? In the absence of new variants that can escape the immune response and cause severe disease in younger people for which we will need new vaccines, our risk groups for severe disease will continue to be the elderly and those with comorbidities. If we are to use booster doses for our population, it is clear that it needs to be a targeted public health intervention to optimally use our resources to protect the most vulnerable.
More importantly, we need to understand that Covid-19 is not going to go away, so if we are to make rational decisions on vaccination and boosting, we need to design and conduct the studies that will give us the answers we need in the shortest possible time. Relying on data from elsewhere to evolve our policy is no longer appropriate for 21st-century India.
Dr Gagandeep Kang
Professor, Christian Medical College, Vellore