ジャーナル: Nat Commun / 年: 2024 タイトル: Quantifying how single dose Ad26.COV2.S vaccine efficacy depends on Spike sequence features. 著者: Craig A Magaret / Li Li / Allan C deCamp / Morgane Rolland / Michal Juraska / Brian D Williamson / James Ludwig / Cindy Molitor / David Benkeser / Alex Luedtke / Brian Simpkins / Fei Heng / ...著者: Craig A Magaret / Li Li / Allan C deCamp / Morgane Rolland / Michal Juraska / Brian D Williamson / James Ludwig / Cindy Molitor / David Benkeser / Alex Luedtke / Brian Simpkins / Fei Heng / Yanqing Sun / Lindsay N Carpp / Hongjun Bai / Bethany L Dearlove / Elena E Giorgi / Mandy Jongeneelen / Boerries Brandenburg / Matthew McCallum / John E Bowen / David Veesler / Jerald Sadoff / Glenda E Gray / Sanne Roels / An Vandebosch / Daniel J Stieh / Mathieu Le Gars / Johan Vingerhoets / Beatriz Grinsztejn / Paul A Goepfert / Leonardo Paiva de Sousa / Mayara Secco Torres Silva / Martin Casapia / Marcelo H Losso / Susan J Little / Aditya Gaur / Linda-Gail Bekker / Nigel Garrett / Carla Truyers / Ilse Van Dromme / Edith Swann / Mary A Marovich / Dean Follmann / Kathleen M Neuzil / Lawrence Corey / Alexander L Greninger / Pavitra Roychoudhury / Ollivier Hyrien / Peter B Gilbert / 要旨: In the ENSEMBLE randomized, placebo-controlled phase 3 trial (NCT04505722), estimated single-dose Ad26.COV2.S vaccine efficacy (VE) was 56% against moderate to severe-critical COVID-19. SARS-CoV-2 ...In the ENSEMBLE randomized, placebo-controlled phase 3 trial (NCT04505722), estimated single-dose Ad26.COV2.S vaccine efficacy (VE) was 56% against moderate to severe-critical COVID-19. SARS-CoV-2 Spike sequences were determined from 484 vaccine and 1,067 placebo recipients who acquired COVID-19. In this set of prespecified analyses, we show that in Latin America, VE was significantly lower against Lambda vs. Reference and against Lambda vs. non-Lambda [family-wise error rate (FWER) p < 0.05]. VE differed by residue match vs. mismatch to the vaccine-insert at 16 amino acid positions (4 FWER p < 0.05; 12 q-value ≤ 0.20); significantly decreased with physicochemical-weighted Hamming distance to the vaccine-strain sequence for Spike, receptor-binding domain, N-terminal domain, and S1 (FWER p < 0.001); differed (FWER ≤ 0.05) by distance to the vaccine strain measured by 9 antibody-epitope escape scores and 4 NTD neutralization-impacting features; and decreased (p = 0.011) with neutralization resistance level to vaccinee sera. VE against severe-critical COVID-19 was stable across most sequence features but lower against the most distant viruses.