The Platform Trial In COVID-19 Priming and BOOsting (PICOBOO): The immunogenicity, reactogenicity, and safety of different COVID-19 vaccinations administered as a second booster (fourth dose) in AZD1222 primed individuals aged 50-<70 years old

Authors:

• McLeod, C.
• Dymock, M.
• Flanagan, K.L.
• Plebanski, M.
• Marshall, H.
• Estcourt, M.J.
• Tjiam, M.C.
• Blyth, C.C.
• Subbarao, K.
• Mordant, F.L.
• Nicholson, S.
• Faust, S.N.
• Wadia, U.
• Thornton, R.B.
• Ellis, Z.
• Mckenzie, A.
• Marsh, J.A.
• Snelling, T.L.
• Richmond, P.

Details:

Journal of Infection, Volume 89, Issue 6, 2024-12-31

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Objectives PICOBOO is a randomised, adaptive trial evaluating the immunogenicity, reactogenicity, and safety of COVID-19 booster strategies. We report data for second boosters among individuals 50-<70 years old primed with AZD1222 (50-<70y-AZD1222) until Day 84. Methods Immunocompetent adults who received any first booster ≥three months prior were eligible. Participants were randomly allocated to BNT162b2, mRNA-1273 or NVX-CoV2373 1:1:1. The concentrations of ancestral anti-spike immunoglobulin were summarised as the geometric mean concentrations (GMC). Reactogenicity and safety outcomes were captured. Additional analyses including neutralising antibodies were performed on a subset. ACTRN12622000238774. Results Between Mar 2022 and Aug 2023, 743 participants were recruited and had D28 samples; 155 belonged to the 50-<70y-AZD1222 stratum. The mean adjusted GMCs (95% credible intervals) were 20,690 (17 555−23 883), 23,867 (20 144−27 604) and 8654 (7267−9962) U/mL at D28 following boosting with BNT162b2, mRNA-1273 and NVX-CoV2372, respectively, and 10,976 (8826−13 196), 15,779 (12 512−19 070) and 6559 (5220−7937) U/mL by D84. IgG against Omicron BA.5 was 2.7–2.9 times lower than the ancestral strain. Limited neutralisation against Omicron subvariants was found following all vaccines. Severe reactogenicity events were <4%. Conclusions All vaccines were immunogenic with more rapid waning after mRNA vaccines. These data support boosting with vaccines with greater specificity for circulating Omicron subvariants.