Munro APS, Janani L, Cornelius V, et al. - In this study, seven different COVID-19 vaccines were tested for reactogenicity and immunogenicity when administered as a third dose after two doses of ChAdOx1 nCov-19 (Oxford–AstraZeneca; hereafter referred to as ChAd) or BNT162b2 (Pfizer–BioNtech, hereafter referred to as BNT); findings revealed all study vaccines augmented antibody and neutralising responses post- ChAd/ChAd initial course and all except one post- BNT/BNT, with no safety issues.

• In this multicentre, randomised, controlled, phase 2 trial (COV-BOOST), individuals aged older than 30 years were enrolled who had received two doses of ChAd or BNT, and had no history of laboratory-confirmed SARS-CoV-2 infection; 2878 eligible participants received COVID-19 vaccine or control.

• Overall increased reactogenicity was noted with three vaccines: m1273 (mRNA1273; Moderna) after ChAd/ChAd or BNT/BNT; and ChAd and Ad26 (Ad26.COV2.S) after BNT/BNT.

• For those who were ChAd/ChAd-primed, spike IgG geometric mean ratios (GMRs) between study vaccines and controls ranged from 1·8 in the half VLA (VLA2001; Valneva) group to 32·3 in the m1273 group.

• For wild-type cellular responses, GMRs relative to controls ranged from 1·1 for ChAd to 3·6 for m1273.

• For BNT/BNT-primed ones, spike IgG GMRs ranged from 1·3 in the half VLA group to 11·5 in the m1273 group; for wild-type cellular responses, GMRs vs controls ranged from 1·0 for half VLA to 4·7 for m1273.

• Outcomes were similar between participants aged 30–69 years and those aged 70 years and older.

• Adverse events (most common solicited were fatigue and pain) occurred more in those aged 30–69 years than those aged 70 years or older.

• Serious adverse events were uncommon, similar in active vaccine and control groups.

• Overall, selection of booster vaccination will be influenced by substantial differences in humoral and cellular responses, and vaccine availability.