The importance of the booster dose to plan ahead

The execution of such a vaccination campaign is what will help get India out of COVID-19’s stranglehold

August 12, 2021 12:02 am | Updated 08:06 am IST

Illustration of vaccine syringes

Illustration of vaccine syringes

The COVID-19 vaccination is relatively new to the world, but the history of vaccination goes back a few centuries. The Expanded Programme on Immunisation was launched by the World Health Organization in 1974 and since then all countries of the world have gained considerable experience in rolling out several vaccines for children and pregnant women.

The immune response

Broadly speaking, vaccines may be classified as replicating live infectious vaccines, and, non-replicating non-infectious vaccines. Currently used live virus vaccines inoculated by injection include measles, rubella, mumps and chickenpox vaccines. The inoculum dose contains a few thousands of live but attenuated viruses — they replicate in body tissues without producing overt disease. The final effective dose that stimulates the immune system may be billions or trillions of viruses and the stimulus sustained for days to weeks as the injected viruses continue to multiply within the human body. Therefore, immune responses to replicating live virus vaccines — both antibody and T-cell immunity — are robust and long-lasting.

Also read | Booster dose: govt bodies deliberate on scientific evidences related to schedule

The non-replicating injected vaccines include nearly all others — the most common being diphtheria, pertussis (whooping cough), tetanus, hepatitis B, Haemophilus influenzae b, pneumococcal, human papilloma virus, inactivated poliovirus, inactivated hepatitis A vaccines. For them, the dose confronted by the immune system is what is injected. What is injected is a tiny amount of antigen, measured in micrograms, plus stabilisers and preservatives in some, and adjuvants in a few, all chemicals and salts in minute quantities.

Why go in for a booster dose

In order to get robust and long-lasting immunity with non-replicating vaccines, we need to give multiple doses — the initial one, two or three doses given in quick succession, at intervals of one or two months, are “priming doses” — meant to prime the immune system to the antigens in the vaccine. The immune system responds well, but with relatively low levels of antibody and subdued T-cell immunity. Over time, in a few months to one year, the antibody levels wane in almost all vaccinated individuals. To reach and maintain high and protective levels of antibody, we need one or more injected “booster dose(s)”.

Every non-replicating vaccine requires priming and boosting. Influenza vaccine boosters are recommended annually; tetanus vaccine once in five to 10 years. For others such as human papilloma and hepatitis A and B vaccines, one booster dose may suffice for decades of protection.

 

All current COVID-19 vaccines fall in the non-replicating category and for robust and long-lasting immunity, they require, quite predictably, priming doses to induce early immunity, and booster dose(s) to sustain, long-term, high antibody titres, overcoming waning immunity.

The current schedules

The current COVID-19 vaccination schedules are only priming doses — the immunity induced by one dose (Johnson & Johnson vaccine), Pfizer vaccine (two doses three weeks apart), all others (two doses at four weeks or more inter-dose interval) are expected to wane, as experience with all previous non-replicating vaccines have taught us. The usual interval between priming and boosting is six months to one year, because protective levels of antibodies will be present for at least that duration, when the priming doses include two or three injections.

Limited experience with antibody titres after natural infection or after vaccination against COVID-19 informs us that the antibody titres decline such that a proportion does not have even detectable virus neutralising antibody levels after six months. There is further evidence that those who are elderly, men particularly, and those with organ transplants, cancer treatment or co-morbidity, have weaker primary antibody responses than their younger/normal counterparts. This implies that they may remain vulnerable to severe disease and death; they are in urgent need for booster dose(s) to ensure and sustain protective immunity.

 

The initial expectation that the COVID-19 pandemic would be a short-lived one is proven wrong. It is now 20 months from the first case and numerous variants have emerged, and chains of transmission continue even in countries which have achieved wide vaccination coverage such as Israel and the United Kingdom. It seems inevitable the pandemic will evolve into a permanent ‘pan-endemic’ state and vaccination is here to stay for years to come, until we manage to eradicate the virus altogether using vaccines.

It is apparently this realisation, that immunity wanes and the pandemic is evolving into endemic long-term prevalence, that prompted Pfizer Company to seek approval for a booster dose in the United States, and Israel’s Ministry of Health to start booster doses to all above 60 years of age.

The strategy ahead

In India, we have an ethical dilemma — as long as there is inadequate vaccine supply, everyone deserves priming doses before even the highly vulnerable early vaccine recipients are offered booster doses. The solution is to accelerate vaccine procurement without counting the cost.

 

For every country planning vaccine roll-out, the science of vaccinology demands that all those getting priming doses should receive at least one booster dose — at a well-chosen interval. The science of immunology teaches us that a booster dose delivered at an interval of at least four, preferably six to 12, months after the last priming dose, will stimulate the production of ‘long-lived’ antibody secreting cells, as well as ‘long lived (virtually life-long) memory cells’. Those who get a third dose one month after the second dose should count it as three-dose priming instead of a true booster which requires four months to one year of wait.

India will do well to plan a vaccination strategy for completing two priming doses in all adults and children, third dose to the special category described above, and one booster dose to everyone one year later. Meticulous planning and the execution of such a vaccination campaign is what will get the country out of the stranglehold of this virus and its variants that have emerged and any that might emerge with higher transmission efficiency than even the Delta.

Dr. T. Jacob John is a retired professor of Clinical Virology, Christian Medical College, Vellore, Tamil Nadu, and a former President of the Indian Academy of Pediatrics. Dr. M.S. Seshadri is a retired professor of Medicine and Clinical Endocrinology, Christian Medical College, Vellore, and currently Medical Director, Thirumalai Mission Hospital, Ranipet, Tamil Nadu

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