Nearly four weeks since Omicron (B.1.1.529) was designated as a variant of concern (VoC), evidence points to its spreading faster than other variants. This is most likely as a result of the ability of the mutated spike protein to bind better to the receptor. It could also be because the virus is able to re-infect previously infected individuals, and infect vaccinated individuals better than other variants. The initial data indicate a lower severity of disease by Omicron. However, that remains to be confirmed as cases accumulate and we develop a better understanding of how the virus behaves in vaccinated and unvaccinated individuals.
Laboratory studies using samples from individuals vaccinated with vaccines made on different platforms, including mRNA, vectored and inactivated vaccines, have reported that the neutralising antibodies are 25 times or much greater times less effective against Omicron than the ancestral strain. Another study from the United Kingdom has reported that two doses of the Oxford-AstraZeneca vaccine (Covishield in India) have limited effectiveness for prevention of symptomatic infection by Omicron, but after a booster dose of an mRNA vaccine, effectiveness goes up to 71%.
Even before the emergence of Omicron, over 80 countries had introduced or planned to introduce booster doses, but the designation of Omicron as a VoC accelerated the process, with countries expanding booster doses for additional age groups or introducing a booster into the immunisation programme, the most notable being South Africa. Alongside, the vaccine manufacturers, particularly those with rapid-response platforms such as mRNA and viral-vectored vaccines, have already begun the vaccine formulation targeted to provide better protection against Omicron.
In India, for the last few months, there has been a demand for COVID-19 booster dose for various population sub-groups. Government-appointed expert committees have been reviewing the need for a booster in India. The start of booster doses in many countries at intervals as short as three months since the start of COVID-19 vaccination in India — and a greater vaccine supply than demand are the arguments being made to support the introduction of booster doses in India. The demand has grown louder with the emergence of Omicron. However, does a new variant make a clear case for the introduction of boosters in India? The answer is not easy, if a scientific approach of basing decisions on data is followed.
The situation is similar to the use of convalescent plasma therapy (CPT) in India. In the early months of the pandemic, CPT was recommended based on plausibility but without any scientific evidence. Later, even when studies reported that it had no or a very limited role in COVID-19 management, it continued to be recommended, using anecdotal evidence from treating physicians or ‘expert’ opinion. There seems to be a similar push for COVID-19 boosters in India, playing out in newspapers and TV debates, but there is no evidence of waning immunity from India to support this approach. Often, selective studies/evidence are/is being quoted, to support the argument one wishes to make; 21 months into the pandemic, any decision on boosters should be based on cumulative scientific evidence examined comprehensively.
Effectiveness of vaccines
On the one hand, pre-print research papers — yet to undergo essential peer scrutiny as a standard part of the scientific process — are being used to argue the case for booster vaccination while on the other, there is a recognition that data from India on vaccines being used in India are very limited. Does the absence of evidence on waning of immunity with Indian vaccines really mean that vaccine immunity is not waning?
For all vaccinations, antibodies rise and then fall. They may fall to undetectable levels, but if they rose at all, then an immune response was made. Should there be a cut-off of the level of antibodies that exactly equated to protection from disease, that would be helpful for tracking the sufficiency of protection. But there is no such correlate of protection for SARS-CoV-2. Data indicate that in general, higher levels of neutralising antibodies indicate greater chances of protection from severe disease and infection, but there is no magic number above which there is assured protection. And this situation is further complicated by variants where antibodies may have different activity against each variant.
Neutralising antibodies are considered functional antibodies; they are the antibodies that block the virus from entering host cells, but there are also many other antibodies that can be found in binding assays that measure whether antibodies can stick to the cognate protein of the virus. The levels of some of these binding antibodies parallel neutralising antibodies, both high or both low, but again there is no cut off that predicts anything about whether the person with high antibodies is truly protected or not.
A recent report on Omicron has good news about another arm of the immune system, showing that T-cell immunity was largely maintained. The spate of laboratory studies further shows that natural infection and vaccination with two doses was approximately equivalent to two doses and a booster. Most of these data are from the mRNA and viral vectored vaccine combinations. We still have a lot to learn about Omicron and the performance of other vaccines in different populations and subpopulations, particularly those in India. It does appear clear that without boosters, protection against infection is likely to be less, but in public health terms, how much this may matter for health-care systems in India remains unquantifiable and unpredictable at this time.
While the evidence on the benefit of boosters is emerging, we also need to worry about the populations that are unvaccinated or partially vaccinated in India and in the world.
A comparison
Offering booster doses will have individual benefit, to a variable extent against different variants. However, when at the global level, vaccines continue to be in short supply, this comes at the cost of a potentially larger benefit for more individuals who still await their primary two doses.
In this backdrop, the decisions on who gets boosters, when and with which vaccine has to be based upon a public health approach, determined by evidence and science.
Second, since every country needs vaccines and access is variable, global access to the first two shots need to be prioritised over boosters for healthy adults. Yes, boosters might ultimately be needed for everyone, but at the moment, we need to immediately consider boosters only for subgroups such as the immunocompromised (often referred to as additional dose as part of an extended primary immunisation schedule) and those at the greatest risk. In India, we must plan and execute real world effectiveness studies at scale in the general population, particularly for those vaccines that have been or will be used mainly or initially in India, so that we can develop an evidence base for decisions on boosters for the general population. This must happen in parallel with increasing the two dose coverage in all adults to the highest possible levels.
Third, we should not be surprised by reports of reinfections and breakthrough infections or of absence of antibodies after natural infection and vaccination, particularly when commercial tests are used. This is expected both because of the design of the tests and as vaccines for mucosal infections, as for SARS-CoV-2, rarely prevent all subsequent infections, but generally continue to protect against severe disease for a longer period.
Fourth, in the context of Omicron, India has an opportunity to plan and implement testing and tracking that will enable an understanding of variant-specific and waning immunity with different vaccines, if we capture infection and vaccination history in people who are affected by this variant.
Fifth, this is an opportunity to review the performance of the vaccine programme and identify the population groups to be prioritised for completion of primary immunisation. It is time for the Government to analyse and use the integrated data from its multiple platforms for decision making.
Every setting is different
India needs a road map that includes COVID-19 testing, provision of care, financial protection, and enhanced science communication with the general public to ensure sustained adherence to COVID-19 appropriate behaviours, and other measures for protection against disease to decrease further disruption by the pandemic. Discussions on boosters are essential, but it is important that India makes its decisions based, as far as possible, on its own data. High seropositivity, as shown in the fourth round of the National Sero-Prevalence Survey, different vaccines from the rest of the world, a different experience with the variants, all indicate that India should not blindly follow the path adopted by other countries and it should determine COVID-19 booster dose policy for the general population based on local evidence and data. In epidemics and pandemics, context matters a lot.
Dr. Chandrakant Lahariya is a physician with advanced training in epidemiology, public health and vaccines and based in New Delhi. Dr. Gagandeep Kang is Professor of Microbiology at Christian Medical College, Vellore, Tamil Nadu
