Covid vaccine boosters: Debates amid dilemma

The ongoing debate on boosters is influenced by science, situational change, sentiment, supplies, solidarity and salesmanship

Not surprising, since the mRNA and virus vector vaccines are spike protein specific, diminishing their efficacy against new spike mutations, while natural infection exposes the immune system to other viral antigens besides the spike.
Not surprising, since the mRNA and virus vector vaccines are spike protein specific, diminishing their efficacy against new spike mutations, while natural infection exposes the immune system to other viral antigens besides the spike.

As Omicron, armed with 32 spike protein mutations, rapidly races across the world, concerns are rising about its implications for India. Respite from the devastating Delta seems to be dissipating as we learn of Omicron’s high transmission rates in Africa and Europe. As numbers begin to rise daily in India, we brace ourselves for a fresh surge of the virus.

Due to this threat, demand for booster doses of vaccines has amplified in the Indian media. Doctors too are asking for additional doses to be given to those who are at high risk of exposure (such as healthcare providers) or at a high risk of severe disease if infected (elderly individuals, immunosuppressed persons and those with co-morbidities). The government says it is still weighing the scientific evidence to decide on whether, when and to whom the administration of extra doses will be permitted.

Nomenclature of boosters is disputed. When clinical trials were conducted for two-dose vaccines, the first was termed the priming dose and the second a booster, as per convention. When a third dose is given, purists would like to call it an ‘extra’ or ‘enhancing’ dose rather than a ‘booster’. However, the term booster for any extra dose is now part of popular parlance. The ongoing debate on boosters is influenced by science, situational change, sentiment, supplies, solidarity and salesmanship. This mix varies across countries and over time.

Scientific studies on vaccine efficacy reveal that: 1) Initially different platforms used for producing Covid vaccines showed high but varying levels of efficacy in clinical trials; (2) currently available vaccines, administered systemically as two doses, do not effectively prevent infection in many but are effective in reducing the risk of severe disease, hospitalisation and death in most of the recipients; (3) With each successive variant of concern (Alpha, Beta, Delta and Omicron), vaccines have shown diminishing efficacy in preventing all forms of clinical illness but retain varied levels of efficacy against severe disease; (4) mRNA vaccines provide very high antibody levels initially but the response fades fast after 4 months for Pfizer’s vaccine and by 6 months for the Moderna vaccine; (5) cellular immunity may still be protective, but difficult to measure (6) boosters with mRNA vaccines show better immune response and clinical protection than boosters with virus vector vaccines; (7) where virus vector vaccines (like AstraZeneca) were used initially, a ‘heterologous’ booster with an mRNA vaccine yields a better immune response than a ‘homologous’ booster with a repeat of the earlier vaccine.

Science has also shown that the immune response varies among the recipients. Individuals who are elderly, malnourished or immunocompromised show a weaker initial response and a faster fadeout of immunity. Persons with co-morbidities, with higher risk of severe disease, form another priority group for boosters when a variant with high immune evasion capability arrives. Persons who had a good immune response too are vulnerable when they are repeatedly exposed to high viral loads after their immunity has faded. Health workers caring for Covid patients fall into this category as they were vaccinated early in 2021.

Prior to Omicron, India was witnessing a diminishing impact of the Delta variant. Government policy was anchored to the goal of completing full vaccination for all adults, before considering adult boosters or child vaccination. With the advent of Omicron, the situation has changed. This variant has high levels of evasion from immunity conferred by two doses of vaccination or by natural infection with any prior form of the virus. A combination of natural infection and vaccination seems to provide the best protection against variants. Not surprising, since the mRNA and virus vector vaccines are spike protein specific, diminishing their efficacy against new spike mutations, while natural infection exposes the immune system to other viral antigens besides the spike.

A belief that many Indians have acquired such ‘hybrid immunity’ this year has guided government strategy thus far. Omicron will test that belief. Even if Omicron results in milder disease than Delta, as reported early on, will that hold good for persons with weak or faded immunity? We are also at a stage where Delta is still around, with Omicron gaining ground but yet to fully sweep Delta aside. A complex situation!

So far India’s children have not been eligible for Covid vaccination, as global experience has shown that infected children have milder clinical effects than adults. Will that assumption hold good for Omicron which is spreading fast among all susceptible population groups? The reported mild nature of Omicron infection, in previously vaccinated adults, may be an argument to extend vaccination now to unvaccinated children instead of prioritising adult boosters.

However, many adults are still partially vaccinated, and some without even a first dose. Should they be covered first before opening the vaccination programme for children? That priority has prevailed so far. Anxiety of parents to protect children when schools are functioning, and the generally caring sentiment of society towards children, may hasten the start of child vaccination. “How long must our kids wait, when other countries are vaccinating theirs?” is the question being asked.

Priorities are easy to reset and vaccination extended to cover both initial vaccination schedules and boosters, for adults and children, if vaccine supplies are as abundant as in the rich countries. Though our supply chain has expanded since August, the two currently used vaccines cannot meet the requirements of such an ambitious vaccination drive on all fronts. So, prioritisation will be necessary. Do we focus on quickly completing double-dose adult vaccination or proceed on two tracks, opening up boosters for vulnerable groups alongside? If the subunit protein vaccines (produced by Serum Institute of India and Biological-E) become available early, and in large quantities, there will be greater elbow room for administering boosters to many. India’s policy of exporting vaccines to other countries, both to meet commercial obligations and to promote vaccine equity through global solidarity, will also influence the domestic supply chain.

Some of the clamour and confusion around boosters comes from the market-savvy statements of vaccine manufacturers. Hardly had the world started digesting the fact that a third dose is needed, when the head of Pfizer announced that a fourth dose too would be required. Clearly, that is a hard sell. The intense burst of immunity from mRNA vaccines seems as short lived as the ardour of a fickle lover. Will other vaccines provide longer duration of protection, besides efficacy, like a devoted suitor? We await these answers while wondering whether each new variant will demand a fresh booster, carrying us from B1 to B12 like the B complex vitamins.

The author, a cardiologist and epidemiologist, is President, Public Health Foundation of India (PHFI). Views are personal

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