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TitleQuantifying how single dose Ad26.COV2.S vaccine efficacy depends on Spike sequence features.
Journal, issue, pagesNat Commun, Vol. 15, Issue 1, Page 2175, Year 2024
Publish dateMar 11, 2024
AuthorsCraig 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 /
PubMed AbstractIn 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.
External linksNat Commun / PubMed:38467646 / PubMed Central
MethodsEM (single particle)
Resolution2.7 - 3.2 Å
Structure data

43658

8vye

EMDB-43658, PDB-8vye:
SARS-CoV-2 S (C.37 Lambda variant) plus S309, S2L20, and S2X303 Fabs
Method: EM (single particle) / Resolution: 2.7 Å

43659

8vyf

EMDB-43659, PDB-8vyf:
SARS-CoV-2 S NTD (C.37 Lambda variant) plus S2L20 and S2X303 Fabs, local refinement
Method: EM (single particle) / Resolution: 3.2 Å

43660

8vyg

EMDB-43660, PDB-8vyg:
SARS-CoV-2 S RBD (C.37 Lambda variant) plus S309 Fab, local refinement
Method: EM (single particle) / Resolution: 3.1 Å

Chemicals

ChemComp-NAG:
2-acetamido-2-deoxy-beta-D-glucopyranose / N-Acetylglucosamine

Source
  • severe acute respiratory syndrome coronavirus 2
  • homo sapiens (human)
KeywordsVIRAL PROTEIN/IMMUNE SYSTEM / sars-cov-2 / coronavirus / lambda / s309 / s2l20 / s2x303 / C.37 / antibody / Fab / S protein / spike / fusion protein / Structural Genomics / Seattle Structural Genomics Center for Infectious Disease / SSGCID / VIRAL PROTEIN / VIRAL PROTEIN-IMMUNE SYSTEM complex

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