The Platform Trial In COVID-19 priming and BOOsting (PICOBOO): The immunogenicity, reactogenicity, and safety of licensed COVID-19 vaccinations administered as a second booster in BNT162b2 primed individuals aged 18-<50 and 50-<70 years old

Objectives: PICOBOO is a randomised, adaptive trial evaluating the immunogenicity, reactogenicity, and safety of COVID-19 booster strategies. Here, we present data for second boosters among individuals aged 18-<50 and 50-<70 years old primed with BNT162b2 until Day (D) 84. Methods: Immunocompetent adults who had received two doses of BNT162b2 and any licensed COVID-19 booster at least three months prior were eligible. Participants were randomly allocated to BNT162b2, mRNA-1273 or NVX-CoV2373 1:1:1. The log(10) concentration of anti-spike Ig Total was summarised as the geometric mean concentration (GMC). Reactogenicity and safety outcomes were captured. Results: Between Mar 2022 and Aug 2023, 743 participants were recruited to the trial and had D28 samples available. Of these, 120 and 103 belonged to the 18-<50 y and 50-<70 y strata, respectively. The mean adjusted GMCs (95% credible intervals) peaked at D28; these were 41 262 (31 611, 51 105), 45 585 (34 194, 57 441) and 25 281 (20 021, 31 234) U/mL in the 18-<50 y stratum and 30 753 (25 071, 36 704), 35 132 (27 523, 42 239) and 17 322 (13 983, 20 641) U/mL in the 50-<70 y stratum following BNT162b2, mRNA-1273 and NVX-CoV2373, respectively. Limited neutralisation against Omicron subvariants was found following boosting with all vaccines. There were 4 possibly or probably-related adverse events in the 18-<50 y stratum and 5 events in the 50-<70 y stratum, and severe reactogenicity events were <10% and <11% in these strata, respectively. Conclusions: Vaccines targeting Ancestral virus elicited boosted antibody responses to Ancestral virus but minimal neutralising antibody against Omicron variants. (c) 2024 Published by Elsevier Ltd on behalf of The British Infection Association. This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/4.0/).