tetano
Editor, Senior Moderator
Nat Commun
. 2024 Mar 11;15(1):2175.
doi: 10.1038/s41467-024-46536-w. Quantifying how single dose Ad26.COV2.S vaccine efficacy depends on Spike sequence features
Craig A Magaret[SUP] 1 [/SUP], Li Li[SUP] 1 [/SUP], Allan C deCamp[SUP] 1 [/SUP], Morgane Rolland[SUP] 2 3 [/SUP], Michal Juraska[SUP] 1 [/SUP], Brian D Williamson[SUP] 1 4 [/SUP], James Ludwig[SUP] 1 [/SUP], Cindy Molitor[SUP] 1 [/SUP], David Benkeser[SUP] 5 [/SUP], Alex Luedtke[SUP] 6 [/SUP], Brian Simpkins[SUP] 7 [/SUP], Fei Heng[SUP] 8 [/SUP], Yanqing Sun[SUP] 9 [/SUP], Lindsay N Carpp[SUP] 1 [/SUP], Hongjun Bai[SUP] 2 3 [/SUP], Bethany L Dearlove[SUP] 2 3 [/SUP], Elena E Giorgi[SUP] 1 [/SUP], Mandy Jongeneelen[SUP] 10 [/SUP], Boerries Brandenburg[SUP] 10 [/SUP], Matthew McCallum[SUP] 11 [/SUP], John E Bowen[SUP] 11 [/SUP], David Veesler[SUP] 11 12 [/SUP], Jerald Sadoff[SUP] 10 [/SUP], Glenda E Gray[SUP] 13 14 [/SUP], Sanne Roels[SUP] 15 [/SUP], An Vandebosch[SUP] 15 [/SUP], Daniel J Stieh[SUP] 10 [/SUP], Mathieu Le Gars[SUP] 10 [/SUP], Johan Vingerhoets[SUP] 15 [/SUP], Beatriz Grinsztejn[SUP] 16 [/SUP], Paul A Goepfert[SUP] 17 [/SUP], Leonardo Paiva de Sousa[SUP] 16 [/SUP], Mayara Secco Torres Silva[SUP] 16 [/SUP], Martin Casapia[SUP] 18 [/SUP], Marcelo H Losso[SUP] 19 [/SUP], Susan J Little[SUP] 20 [/SUP], Aditya Gaur[SUP] 21 [/SUP], Linda-Gail Bekker[SUP] 22 [/SUP], Nigel Garrett[SUP] 23 24 [/SUP], Carla Truyers[SUP] 15 [/SUP], Ilse Van Dromme[SUP] 15 [/SUP], Edith Swann[SUP] 25 [/SUP], Mary A Marovich[SUP] 25 [/SUP], Dean Follmann[SUP] 26 [/SUP], Kathleen M Neuzil[SUP] 27 [/SUP], Lawrence Corey[SUP] 1 28 [/SUP], Alexander L Greninger[SUP] 1 11 [/SUP], Pavitra Roychoudhury[SUP] 1 11 [/SUP], Ollivier Hyrien[SUP] 1 [/SUP], Peter B Gilbert[SUP] 29 30 31 [/SUP]
Affiliations
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.
. 2024 Mar 11;15(1):2175.
doi: 10.1038/s41467-024-46536-w. Quantifying how single dose Ad26.COV2.S vaccine efficacy depends on Spike sequence features
Craig A Magaret[SUP] 1 [/SUP], Li Li[SUP] 1 [/SUP], Allan C deCamp[SUP] 1 [/SUP], Morgane Rolland[SUP] 2 3 [/SUP], Michal Juraska[SUP] 1 [/SUP], Brian D Williamson[SUP] 1 4 [/SUP], James Ludwig[SUP] 1 [/SUP], Cindy Molitor[SUP] 1 [/SUP], David Benkeser[SUP] 5 [/SUP], Alex Luedtke[SUP] 6 [/SUP], Brian Simpkins[SUP] 7 [/SUP], Fei Heng[SUP] 8 [/SUP], Yanqing Sun[SUP] 9 [/SUP], Lindsay N Carpp[SUP] 1 [/SUP], Hongjun Bai[SUP] 2 3 [/SUP], Bethany L Dearlove[SUP] 2 3 [/SUP], Elena E Giorgi[SUP] 1 [/SUP], Mandy Jongeneelen[SUP] 10 [/SUP], Boerries Brandenburg[SUP] 10 [/SUP], Matthew McCallum[SUP] 11 [/SUP], John E Bowen[SUP] 11 [/SUP], David Veesler[SUP] 11 12 [/SUP], Jerald Sadoff[SUP] 10 [/SUP], Glenda E Gray[SUP] 13 14 [/SUP], Sanne Roels[SUP] 15 [/SUP], An Vandebosch[SUP] 15 [/SUP], Daniel J Stieh[SUP] 10 [/SUP], Mathieu Le Gars[SUP] 10 [/SUP], Johan Vingerhoets[SUP] 15 [/SUP], Beatriz Grinsztejn[SUP] 16 [/SUP], Paul A Goepfert[SUP] 17 [/SUP], Leonardo Paiva de Sousa[SUP] 16 [/SUP], Mayara Secco Torres Silva[SUP] 16 [/SUP], Martin Casapia[SUP] 18 [/SUP], Marcelo H Losso[SUP] 19 [/SUP], Susan J Little[SUP] 20 [/SUP], Aditya Gaur[SUP] 21 [/SUP], Linda-Gail Bekker[SUP] 22 [/SUP], Nigel Garrett[SUP] 23 24 [/SUP], Carla Truyers[SUP] 15 [/SUP], Ilse Van Dromme[SUP] 15 [/SUP], Edith Swann[SUP] 25 [/SUP], Mary A Marovich[SUP] 25 [/SUP], Dean Follmann[SUP] 26 [/SUP], Kathleen M Neuzil[SUP] 27 [/SUP], Lawrence Corey[SUP] 1 28 [/SUP], Alexander L Greninger[SUP] 1 11 [/SUP], Pavitra Roychoudhury[SUP] 1 11 [/SUP], Ollivier Hyrien[SUP] 1 [/SUP], Peter B Gilbert[SUP] 29 30 31 [/SUP]
Affiliations
- PMID: 38467646
- 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.