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

• Published in: Nature communications Vol. 15; no. 1; pp. 2175 - 22
• Main Authors: Magaret, Craig A, Li, Li, deCamp, Allan C, Rolland, Morgane, Juraska, Michal, Williamson, Brian D, Ludwig, James, Molitor, Cindy, Benkeser, David, Luedtke, Alex, Simpkins, Brian, Heng, Fei, Sun, Yanqing, Carpp, Lindsay N, Bai, Hongjun, Dearlove, Bethany L, Giorgi, Elena E, Jongeneelen, Mandy, Brandenburg, Boerries, McCallum, Matthew, Bowen, John E, Veesler, David, Sadoff, Jerald, Gray, Glenda E, Roels, Sanne, Vandebosch, An, Stieh, Daniel J, Le Gars, Mathieu, Vingerhoets, Johan, Grinsztejn, Beatriz, Goepfert, Paul A, de Sousa, Leonardo Paiva, Silva, Mayara Secco Torres, Casapia, Martin, Losso, Marcelo H, Little, Susan J, Gaur, Aditya, Bekker, Linda-Gail, Garrett, Nigel, Truyers, Carla, Van Dromme, Ilse, Swann, Edith, Marovich, Mary A, Follmann, Dean, Neuzil, Kathleen M, Corey, Lawrence, Greninger, Alexander L, Roychoudhury, Pavitra, Hyrien, Ollivier, Gilbert, Peter B
• Format: Journal Article
• Language: English
• Published: England Nature Publishing Group 11.03.2024; Nature Publishing Group UK; Nature Portfolio
• Subjects: Ad26COVS1; Amino Acids; Antibodies; Antibodies, Neutralizing; Antibodies, Viral; COVID-19; COVID-19 - prevention & control; COVID-19 vaccines; Effectiveness; Epitopes; Humans; Neutralization; Pandemics; Placebos; SARS-CoV-2; Severe acute respiratory syndrome coronavirus 2; Vaccine Efficacy; Vaccines; Viral diseases; Latin America
• ISSN: 2041-1723; 2041-1723
• DOI: 10.1038/s41467-024-46536-w

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.