COV-BOOST: evidence to support rapid booster deployment

With accruing evidence that the effectiveness of COVID-19 vaccines wanes over time,1, 2, 3, 4 and the recent emergence of the omicron (B.1.1.529) variant,⁵ some countries are rapidly deploying vaccine boosters.⁶ In the UK, the COVID-19 vaccination campaign launched in December, 2020, and began with prioritised population groups, including people most likely to be at higher risk for severe outcomes or those providing health services or care for these individuals. With emerging evidence from Israel and the UK of vaccine waning, the Joint Committee on Vaccination and Immunisation (JCVI) in September, 2021, recommended boosting individuals in a phased way 6 months after completion of their primary course of COVID-19 immunisation.⁷ Additionally, with concerns around the mutational profile of omicron, with WHO designating it a variant of concern on Nov 26, 2021,⁵ acceleration of a third dose in the UK was proposed as a key response strategy for COVID-19, resulting in widening eligibility to all people aged 18 years and older and reducing the minimum time interval between doses two and three.8, 9

In The Lancet, Alasdair Munro and colleagues¹⁰ report the outcomes of the COV-BOOST trial, which is timely and provides valuable evidence on the immunogenicity and safety of seven COVID-19 vaccines administered as boosters. This multicentre UK trial recruited 2878 healthy participants older than 30 years across 18 sites who had received either two doses of BNT162b2 or ChAdOx1 nCov-19, with no history of previous SARS-CoV-2 infection, and randomly assigned them to receive one of seven COVID-19 vaccines; namely, NVX-CoV2373 (Novavax, NVX), ChAdOx1 nCov-19 (Oxford–AstraZeneca, ChAd), BNT162b2 (Pfizer–BioNtech, BNT), VLA2001 (Valneva, VLA), Ad26.COV2.S (Janssen), mRNA1273 (Moderna, m1273), CVnCov (CureVac), three of which were also used as half doses (BNT, VLA, and NVX) or a quadrivalent meningococcal conjugate vaccine (MenACWY) as a control. The coprimary outcomes were safety and immunogenicity of anti-spike IgG measured by ELISA at day 28. In the ChAd/ChAd-primed participants, the median age was 53 years (IQR 44–61) in the younger group and 76 years (73–78) in the older group. In the BNT/BNT-primed participants, the median age was 51 years (41–59) in the younger group and 78 years (75–82) in the older group. In the ChAd/ChAD-primed group, 676 (46·7%) participants were female and 1380 (95·4%) were white, and in the BNT/BNT-primed group 770 (53·6%) participants were female and 1321 (91·9%) were white.

Munro and colleagues¹⁰ report that vaccines were effective in boosting neutralising antibody and cellular responses within 28 days of administration. They also identify no safety concerns and the profiles of side-effects were similar to those seen with the primary course across all vaccines, which should inform public health messaging on boosters, or third doses, and provide reassurance. The more detailed data on variability in immunogenicity and side-effect profiles by vaccine type are valuable to inform decisions on booster regimens, alongside considerations of vaccine availability and population primary vaccine course regimens. ChAd, BNT, and m1273 demonstrated significantly increased cellular responses geometric mean ratio to the beta (B.1.351) strain within 14 days, for either primary course, which one would hope would be similar to the responses seen with omicron.

COV-BOOST was a robustly conducted study and therefore provides strong evidence that these vaccine boosters are immunogenic and safe, in a trial context, among healthy adult participants older than 30 years. The inclusion of seven different COVID-19 vaccines provides options for adapting regimens according to supply and ensure the findings are relevant to varied global communities. The finding of rapid boosting supports the recent UK decision to expand access to third doses as a precaution to increase population protection against the omicron variant, although more time and evidence are required to gain a fuller understanding of the performance of COVID-19 vaccines against this new variant. While recognising that longer intervals between dose two and three are likely to be more immunogenic,¹¹ the dosing interval in this study was shortened by necessity (minimum 70 days for ChAd, 84 days for BNT), and therefore provides evidence of effect at shorter intervals, which has informed the UK decision following the emergence of omicron to shorten the minimum interval between second and third doses from 6 months to 3 months.

Understandably, as a clinical trial, there are limitations, chiefly in the generalisability of findings beyond the trial setting, particularly to younger populations, those with previous SARS-CoV-2 infection, and to recipients of different primary course regimens, and in assessing impacts, of both safety and effectiveness, at scale and longer follow-up. The latter point highlights the complementarity between clinical trials, observational studies, and surveillance, with large cohort studies well placed to determine whether the immunogenicity generated after boosters translates to real-world protection from SARS-CoV-2 infection, and ongoing surveillance essential to detect potential rare adverse events.

Finally, we consider it necessary to highlight that although the focus in highly vaccinated high-income countries like the UK is currently on boosters, only 6% of people in low-income countries have received at least one dose.⁶ In addition to efforts to increase vaccine affordability and access globally, it is important to ensure that COVID-19 vaccination and research are inclusive. For many low-income countries with high seroprevalence after infection, the focus must be maintained on rapidly giving the first and second doses of COVID-19 vaccine to boost immunity gained from primary infection, endorsing the WHO targets to vaccinate 40% of the global population by the end of 2021 and 70% by mid-2022.¹²

© 2021 Leon Neal/Getty Images

SH and VH declare funding from UK Department of Health and Social Care (with contributions from Governments in Northern Ireland, Wales, and Scotland) and the National Institutes for Health Research, and grant funding from the Medical Research Council for the SIREN Study.