Considerations in boosting COVID-19 vaccine immune responses - The Lancet
▻https://www.thelancet.com/journals/lancet/article/PIIS0140-6736(21)02046-8/fulltext
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A new wave of COVID-19 cases caused by the highly transmissible delta variant is exacerbating the worldwide public health crisis, and has led to consideration of the potential need for, and optimal timing of, booster doses for vaccinated populations.1
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. COVID-19 vaccines continue to be effective against severe disease, including that caused by the delta variant. Most of the observational studies on which this conclusion is based are, however, preliminary and difficult to interpret precisely due to potential confounding and selective reporting. Careful and public scrutiny of the evolving data will be needed to assure that decisions about boosting are informed by reliable science more than by politics. Even if boosting were eventually shown to decrease the medium-term risk of serious disease, current vaccine supplies could save more lives if used in previously unvaccinated populations than if used as boosters in vaccinated populations.
Boosting could be appropriate for some individuals in whom the primary vaccination, defined here as the original one-dose or two-dose series of each vaccine, might not have induced adequate protection—eg, recipients of vaccines with low efficacy or those who are immunocompromised2
(although people who did not respond robustly to the primary vaccination might also not respond well to a booster). It is not known whether such immunocompromised individuals would receive more benefit from an additional dose of the same vaccine or of a different vaccine that might complement the primary immune response.
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Boosting might ultimately be needed in the general population because of waning immunity to the primary vaccination or because variants expressing new antigens have evolved to the point at which immune responses to the original vaccine antigens no longer protect adequately against currently circulating viruses.
Although the benefits of primary COVID-19 vaccination clearly outweigh the risks, there could be risks if boosters are widely introduced too soon, or too frequently, especially with vaccines that can have immune-mediated side-effects (such as myocarditis, which is more common after the second dose of some mRNA vaccines,3
or Guillain-Barre syndrome, which has been associated with adenovirus-vectored COVID-19 vaccines4
). If unnecessary boosting causes significant adverse reactions, there could be implications for vaccine acceptance that go beyond COVID-19 vaccines. Thus, widespread boosting should be undertaken only if there is clear evidence that it is appropriate.
Current evidence does not, therefore, appear to show a need for boosting in the general population, in which efficacy against severe disease remains high. Even if humoral immunity appears to wane, reductions in neutralising antibody titre do not necessarily predict reductions in vaccine efficacy over time, and reductions in vaccine efficacy against mild disease do not necessarily predict reductions in the (typically higher) efficacy against severe disease. This effect 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.5
The ability of vaccines that present the antigens of earlier phases of the pandemic (rather than variant-specific antigens) to elicit humoral immune responses against currently circulating variants6
, 7
indicates that these variants have not yet evolved to the point at which they are likely to escape the memory immune responses induced by those vaccines. Even without any changes in vaccine efficacy, increasing success in delivering vaccines to large populations will inevitably lead to increasing numbers of breakthrough cases, especially if vaccination leads to behavioural changes in vaccinees.
The message that boosting might soon be needed, if not justified by robust data and analysis, could adversely affect confidence in vaccines and undermine messaging about the value of primary vaccination. Public health authorities should also carefully consider the consequences for primary vaccination campaigns of endorsing boosters only for selected vaccines. Booster programmes that affect some but not all vaccinees may be difficult to implement—so it will be important to base recommendations on complete data about all vaccines available in a country, to consider the logistics of vaccination, and to develop clear public health messaging before boosting is widely recommended.