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Publication Abstract from PubMed

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.

Quantifying how single dose Ad26.COV2.S vaccine efficacy depends on Spike sequence features.,Magaret CA, Li L, deCamp AC, Rolland M, Juraska M, Williamson BD, Ludwig J, Molitor C, Benkeser D, Luedtke A, Simpkins B, Heng F, Sun Y, Carpp LN, Bai H, Dearlove BL, Giorgi EE, Jongeneelen M, Brandenburg B, McCallum M, Bowen JE, Veesler D, Sadoff J, Gray GE, Roels S, Vandebosch A, Stieh DJ, Le Gars M, Vingerhoets J, Grinsztejn B, Goepfert PA, de Sousa LP, Silva MST, Casapia M, Losso MH, Little SJ, Gaur A, Bekker LG, Garrett N, Truyers C, Van Dromme I, Swann E, Marovich MA, Follmann D, Neuzil KM, Corey L, Greninger AL, Roychoudhury P, Hyrien O, Gilbert PB Nat Commun. 2024 Mar 11;15(1):2175. doi: 10.1038/s41467-024-46536-w. PMID:38467646^[1]

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.