By Mary Hearty

At the moment, COVID-19 vaccine booster doses for the general public are not appropriate as vaccines remain highly effective against severe disease, including that from the main viral variants.

An expert review by an international group of scientists, including some at the World Health Organization (WHO) and Food and Drug Administration (FDA) affirmed this after evaluating the currently available evidence from randomized controlled trials and observational studies published in The Lancet peer-reviewed journals and pre-print servers.

According to the findings reported from the observational studies, vaccination had 95% efficacy against severe disease from both the delta variant and alpha variant, and over 80% efficacy at protecting against any infection from these variants.

The authors stated that the ability of vaccines to elicit an antibody response against current variants indicates that these variants have not yet evolved to the point at which they are likely to escape the memory immune response induced by the vaccines.

According to the experts, even if new variants that can escape the current vaccines are going to evolve, they are most likely to do so from strains that have already become widely prevalent.

Therefore, the effectiveness of boosters developed specifically to match potential newer variants could be greater and longer-lived than boosters using current vaccines.

A similar strategy is used for influenza vaccines, for which each annual vaccine is based on the most current data about circulating strains, increasing the likelihood that the vaccine will remain effective even if there is further strain evolution.

Nevertheless, if boosters are ultimately to be used, there will be a need to identify specific circumstances where the benefits outweigh the risks.

For instance, Dr. Katherine O’Brien during WHO’s Science in 5 interview on COVID-19 vaccine booster shots highlighted three reasons why people might be given an additional dose.

The first is if one did not respond to the first two doses, like immuno-compromised people, then it may be necessary to receive a third dose, unlike normal, healthy people.

The second reason Dr. O’Brien mentioned: “if over time the immunity that you received and achieved as a result of being vaccinated starts to wane, it starts to deteriorate or go down over time.”

The third scenario is if the performances of the vaccines are less or inadequate against some of the variants of concern that have emerged, adding that the available vaccines are holding up well against the severe end of the disease spectrum. So, we do not see strong evidence leading to a need to provide a third dose for people who have already been vaccinated, she said.

The authors’ review published in The Lancet also noted that across all vaccine types and variants, vaccine efficacy is greater against severe disease than against mild disease.

Although vaccines are less effective against asymptomatic disease or against transmission than against severe disease, even in populations with high vaccination coverage the unvaccinated minority are still the major drivers of transmission, as well as being at the highest risk of serious disease.

Even without any loss of vaccine efficacy, however, increasing success in delivering vaccines to large populations will inevitably lead to increasing numbers of vaccinated people, decreasing numbers of unvaccinated people, and hence an increasing proportion of all cases being breakthrough cases, especially if vaccination leads to behavioral changes in vaccines.

This raises a great concern in places like Africa which is still grappling with slow and low vaccine rollout due to issues such as vaccine hesitancy and inequity in most of the countries, hence posing further evolution of variants. As a result, its population could be at the highest risk of serious disease.

Moreover, evidence from research led by the University of Southampton on the uptake of the COVID-19 vaccination in Ghana concluded that vaccine hesitancy is influenced by lack of adequate information, with some believing the vaccine to be dangerous and others mistrusting the government.

Dr Ken Brackstone, report author and Research Fellow at the University of Southampton during a media briefing with Africa Science Media Centre (AfriSMC) said: “Proactive health promotion and public health messaging is vital to reassure the Ghanaian general public about vaccine safety. Vaccine supply to Ghana and the rest of sub-Saharan Africa is too slow and when supplies do arrive, they will undoubtedly be limited, so it’s imperative that they end up in people’s arms.”

Prof Walter Jaoko, Director of KAVI-Institute of Clinical Research and Professor of Medical Microbiology from the University of Nairobi advised: “We must not put off getting vaccinated just because of our concerns about new variants. We must keep on with vaccination even if we are trying to see whether the vaccines are less effective against some variants. We must continue using the tools in hand as we improve them.”

Prof Jaoko added: “We need more people vaccinated, less virus circulation, and that will result in fewer mutations and less variants.”

Additionally, taken as a whole, the currently available studies do not provide credible evidence of substantially declining protection against severe disease, which is the primary goal of vaccination.

“The limited supply of these vaccines will save the most lives if made available to people who are at appreciable risk of serious disease and have not yet received any vaccine. Even if some gain can ultimately be obtained from boosting, it will not outweigh the benefits of providing initial protection to the unvaccinated,” Dr. Ana-Maria Henao-Restrepo, WHO and the lead author of the review published in The Lancet said.

According to Dr Henao-Restrepo, if vaccines are deployed where they would do the most good, they could hasten the end of the pandemic by inhibiting further evolution of variants.

Moreover, the authors acknowledged that even if levels of antibodies in vaccinated individuals wane over time, this does not necessarily predict reductions in the efficacy of vaccines against severe disease.

This could be because protection against severe disease is mediated not only by antibody responses, which might be relatively short-lived for some vaccines, but also by memory responses and cell-mediated immunity, which are generally longer-lived.

Dr Soumya Swaminathan, WHO Chief Scientist stated: “The vaccines that are currently available are safe, effective, and save lives. Although the idea of further reducing the number of COVID-19 cases by enhancing immunity in vaccinated people is appealing, any decision to do so should be evidence-based and consider the benefits and risks for individuals and society. These high-stakes decisions should be based on robust evidence and international scientific discussion.”