Quantifying how single dose Ad26.COV2.S vaccine efficacy depends on Spike sequence features

Magaret C.A.; Li L.; deCamp A.C.; Rolland M.; Juraska M.; Williamson B.D.; Ludwig J.; Molitor C.; Benkeser D.; Luedtke A.; Simpkins B.; Heng F.; Sun Y.; Carpp L.N.; Bai H.; Dearlove B.L.; Giorgi E.E.; Jongeneelen M.; Brandenburg B.; McCallum M.; Bowen J.E.; Veesler D.; Sadoff J.; Gray G.E.; Roels S.; Vandebosch A.; Stieh D.J.; Le Gars M.; Vingerhoets J.; Grinsztejn B.; Goepfert P.A.; de Sousa L.P.; Silva M.S.T.; Casapia M.; Losso M.H.; Little S.J.; Gaur A.; Bekker L.-G.; Garrett N.; Truyers C.; Van Dromme I.; Swann E.; Marovich M.A.; Follmann D.; Neuzil K.M.; Corey L.; Greninger A.L.; Roychoudhury P.; Hyrien O.; Gilbert P.B. · Nature Communications (2024) · DOI: 10.1038/s41467-024-46536-w

Resumen

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. © The Author(s) 2024.