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QUANTIFYING HOW SINGLE DOSE AD26.COV2.S VACCINE EFFICACY DEPENDS ON SPIKE SEQUENCE FEATURES
Magaret, Craig et al. | Date Issued: 2023
Author
Magaret, Craig
Li, Li
deCamp, Allan
Rolland, Morgane
Juraska, Michal
Williamson, Brian
Ludwig, James
Molitor, Cindy
Benkeser, David
Luedtke, Alex
Simpkins, Brian
Carpp, Lindsay
Bai, Hongjun
Deariove, Bethany
Greninger, Alexander
Roychoudhury, Pavitra
Sadoff, Jerald
Gray, Glenda
Roels, Sanne
Vandebosch, An
Stieh, Daniel
Gars, Mathieu Le
Vingerhoets, Johan
Grinsztejn, Beatriz
Goepfert, Paul
Truyers, Carla
Dromme, Ilse Van
Swann, Edith
Marovich, Mary
Follmann, Dean
Neuzil, Kathleen
Corey, Lawrence
Hyrien, Ollivier
Sousa, Leonardo Paiva de
Casapia, Martin
Losso, Marcelo
Little, Susan
Gaur, Aditya
Bekker, Linda-Gail
Garrett, Nigel
Heng, Fei
Sun, Yanqing
Gilbert, Peter
Affilliation
Fred Hutchinson Cancer Center. Seattle, Washington, USA.
Fred Hutchinson Cancer Center. Seattle, Washington, USA.
Fred Hutchinson Cancer Center. Seattle, Washington, USA.
MHRP-HJF.
Fred Hutchinson Cancer Center. Seattle, Washington, USA.
Kaiser Permanente Washington Health Research Institute. Seattle, Washington, USA.
Fred Hutchinson Cancer Center. Seattle, Washington, USA.
Fred Hutchinson Cancer Center. Seattle, Washington, USA.
Emory.
University of Washington. Seattle, Washington, USA.
Pitzer College. Claremont, CA, USA.
Fred Hutchinson Cancer Center. Seattle, Washington, USA.
Walter Reed Army Institute of Research. Silver Spring, MD, USA.
Walter Reed Army Institute of Research. Silver Spring, MD, USA.
University of Washington. Seattle, Washington, USA.
University of Washington. Seattle, Washington, USA.
Janssen Research & Development. LLC. Raritan, Nova Jersey, USA.
South African Medical Research Council. Francie van Zijl Drive, Parow Valley, Cape Town.
Janssen Research & Development. LLC. Raritan, Nova Jersey, USA.
Janssen Research & Development. LLC. Raritan, Nova Jersey, USA.
Janssen Vaccines & Prevention BV. Leiden, Netherlands.
Janssen Vaccines & Prevention BV. Leiden, Netherlands.
Janssen Pharmaceutica N.V. Beerse, Belgium.
Fundação Oswaldo Cruz. Instituto Nacional de Infectologia Evandro Chagas. Laboratório de Pesquisa Clínica em DST e AIDS. Rio de Janeiro, RJ, Brasil.
University of Alabama at Birmingham. Department of Medicine. Division of Infectious Diseases. Birmingham, AL, USA.
Janssen Pharmaceutica N.V. Beerse, Belgium.
Janssen R&D. Division of Janssen Pharmaceutica NV. Beerse, Belgium.
National Institute of Allergy and Infectious Diseases. Maryland, USA.
National Institute of Allergy and Infectious Diseases. Maryland, USA.
National Institutes of Health. Maryland, USA.
University of Maryland School of Medicine. Baltimore, MD, USA.
Fred Hutchinson Cancer Center. Seattle, Washington, USA.
Fred Hutchinson Cancer Research Center. Seattle, WA, USA.
Oswaldo Cruz Foundation. Evandro Chagas National Institute of Infectious Diseases. Rio de Janeiro, RJ, Brazil.
Asociación Civil Selva Amazónica. Iquitos, Peru.
Hospital General de Agudos José María Ramos Mejia. Buenos Aires, Argentina.
University of California. Department of Medicine. San Diego, CA, USA.
St. Jude Children's Research Hospital. Memphis, TN, USA.
Desmond Tutu HIV Centre. Cape Town, South Africa.
University of KwaZulu-Natal. Centre for the AIDS Program of Research in South Africa. Durban, South Africa.
University of North Florida. Jacksonville, FL, USA.
University of North Carolina at Charlotte. Charlotte, NC, USA.
Fred Hutchinson Cancer Center. Seattle, Washington, USA.
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.
Keywords
Antibody-epitope escape score
COVID-19
ENSEMBLE trial
Hamming distance
SARS-CoV-2
Genetic distance
Neutralization resistance
Sieve analysis
Vaccine efficacy
Viral variants
 
Publisher
Janssen Research & Development
Citation
MAGARET, Craig et al. Quantifying how single dose Ad26.COV2.S vaccine efficacy depends on Spike sequence features. Research Square, p. 1-25, May 2023.
DOI
10.21203/rs.3.rs-2743022/v1
ISSN
2693-5015