Quantifying how single dose Ad26.COV2.S vaccine efficacy depends on Spike sequence features
Abstract
It is of interest to pinpoint SARS-CoV-2 sequence features defining vaccine resistance. In the ENSEMBLE randomized, placebo-controlled phase 3 trial, estimated single-dose Ad26.COV2.S vaccine efficacy (VE) was 56% against moderate to severe–critical COVID-19. SARS-CoV-2 Spike sequences were measured from 484 vaccine and 1,067 placebo recipients who acquired COVID-19 during the trial. In Latin America, where Spike diversity was greatest, VE was significantly lower against Lambda than against Reference and against all non-Lambda variants [family-wise error rate (FWER) p < 0.05]. VE also differed by residue match vs. mismatch to the vaccine-strain residue at 16 amino acid positions (4 FWER p < 0.05; 12 q-value ≤ 0.20). VE 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 different antibody-epitope escape scores and by 4 NTD neutralization-impacting features; and decreased (p = 0.011) with neutralization resistance level to vaccine recipient sera. VE against severe–critical COVID-19 was stable across most sequence features but lower against viruses with greatest distances. These results help map antigenic specificity of in vivo vaccine protection.
Document Details
- Document Type
- Pub Defense Publication
- Publication Date
- May 31, 2023
- Source ID
- 10.21203/rs.3.rs-2743022/v1
Entities
People
- Aditya Gaur
- Alex Luedtke
- Alexander L. Greninger
- Allan C deCamp
- An Vandebosch
- Beatriz Grinsztejn
- Bethany L Dearlove
- Brian D Williamson
- Brian Simpkins
- Carla Truyers
- Cindy Molitor
- Craig A Magaret
- Daniel Stieh
- David Benkeser
- Dean Follmann
- Edith M Swann
- Fei Heng
- Glenda Gray
- Hongjun Bai
- Ilse Van Dromme
- James P. Ludwig
- Jerald Sadoff
- Johan Vingerhoets
- Kathleen Neuzil
- Lawrence Corey
- Leonardo Paiva de Sousa
- Li Li
- Linda-Gail Bekker
- Lindsay N Carpp
- Marcelo Losso
- Martín Casapía
- Mary Marovich
- Mathieu Le Gars
- Michal Juraska
- Morgane Rolland
- Nigel Garrett
- Ollivier Hyrien
- Paul Goepfert
- Pavitra Roychoudhury
- Peter B Gilbert
- Sanne Roels
- Susan J Little
- Yanqing Sun
Organizations
- Emory and Henry University
- Fred Hutchinson Cancer Center
- Janssen Pharmaceutica
- Janssen Vaccines
- Kaiser Permanente
- National Institute of Allergy and Infectious Diseases
- National Institutes of Health
- Pitzer College
- South African Medical Research Council
- St. Jude Children's Research Hospital
- University of Alabama at Birmingham
- University of California
- University of KwaZulu-Natal
- University of Maryland School of Medicine
- University of North Carolina at Charlotte
- University of North Florida
- University of Washington
- Walter Reed Army Institute of Research