Nature Communications (Mar 2024)
Quantifying how single dose Ad26.COV2.S vaccine efficacy depends on Spike sequence features
- Craig 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
Affiliations
- Craig A. Magaret
- Vaccine and Infectious Disease Division, Fred Hutchinson Cancer Center
- Li Li
- Vaccine and Infectious Disease Division, Fred Hutchinson Cancer Center
- Allan C. deCamp
- Vaccine and Infectious Disease Division, Fred Hutchinson Cancer Center
- Morgane Rolland
- US Military HIV Research Program, Walter Reed Army Institute of Research
- Michal Juraska
- Vaccine and Infectious Disease Division, Fred Hutchinson Cancer Center
- Brian D. Williamson
- Vaccine and Infectious Disease Division, Fred Hutchinson Cancer Center
- James Ludwig
- Vaccine and Infectious Disease Division, Fred Hutchinson Cancer Center
- Cindy Molitor
- Vaccine and Infectious Disease Division, Fred Hutchinson Cancer Center
- David Benkeser
- Departments of Biostatistics and Bioinformatics, Rollins School of Public Health, Emory University
- Alex Luedtke
- Department of Statistics, University of Washington
- Brian Simpkins
- Department of Computer Science, Pitzer College
- Fei Heng
- University of North Florida
- Yanqing Sun
- University of North Carolina at Charlotte
- Lindsay N. Carpp
- Vaccine and Infectious Disease Division, Fred Hutchinson Cancer Center
- Hongjun Bai
- US Military HIV Research Program, Walter Reed Army Institute of Research
- Bethany L. Dearlove
- US Military HIV Research Program, Walter Reed Army Institute of Research
- Elena E. Giorgi
- Vaccine and Infectious Disease Division, Fred Hutchinson Cancer Center
- Mandy Jongeneelen
- Johnson & Johnson Innovative Medicine, Janssen Vaccines & Prevention B.V
- Boerries Brandenburg
- Johnson & Johnson Innovative Medicine, Janssen Vaccines & Prevention B.V
- Matthew McCallum
- Department of Biochemistry, University of Washington
- John E. Bowen
- Department of Biochemistry, University of Washington
- David Veesler
- Department of Biochemistry, University of Washington
- Jerald Sadoff
- Johnson & Johnson Innovative Medicine, Janssen Vaccines & Prevention B.V
- Glenda E. Gray
- Perinatal HIV Research Unit, Faculty of Health Sciences, University of the Witwatersrand
- Sanne Roels
- Janssen R&D, a division of Janssen Pharmaceutica NV
- An Vandebosch
- Janssen R&D, a division of Janssen Pharmaceutica NV
- Daniel J. Stieh
- Johnson & Johnson Innovative Medicine, Janssen Vaccines & Prevention B.V
- Mathieu Le Gars
- Johnson & Johnson Innovative Medicine, Janssen Vaccines & Prevention B.V
- Johan Vingerhoets
- Janssen R&D, a division of Janssen Pharmaceutica NV
- Beatriz Grinsztejn
- Evandro Chagas National Institute of Infectious Diseases-Fundação Oswaldo Cruz
- Paul A. Goepfert
- Division of Infectious Diseases, Department of Medicine, University of Alabama at Birmingham
- Leonardo Paiva de Sousa
- Evandro Chagas National Institute of Infectious Diseases-Fundação Oswaldo Cruz
- Mayara Secco Torres Silva
- Evandro Chagas National Institute of Infectious Diseases-Fundação Oswaldo Cruz
- Martin Casapia
- Facultad de Medicina Humana, Universidad Nacional de la Amazonia Peru
- Marcelo H. Losso
- Hospital General de Agudos José María Ramos Mejia
- Susan J. Little
- Division of Infectious Diseases, University of California San Diego
- Aditya Gaur
- Department of Infectious Diseases, St. Jude Children’s Research Hospital
- Linda-Gail Bekker
- The Desmond Tutu HIV Centre, University of Cape Town, Observatory
- Nigel Garrett
- Centre for the AIDS Programme of Research in South Africa, University of KwaZulu-Natal
- Carla Truyers
- Janssen R&D, a division of Janssen Pharmaceutica NV
- Ilse Van Dromme
- Janssen R&D, a division of Janssen Pharmaceutica NV
- Edith Swann
- Vaccine Research Program, Division of AIDS, National Institute of Allergy and Infectious Diseases, National Institutes of Health
- Mary A. Marovich
- Vaccine Research Program, Division of AIDS, National Institute of Allergy and Infectious Diseases, National Institutes of Health
- Dean Follmann
- Biostatistics Research Branch, National Institute of Allergy and Infectious Diseases, National Institutes of Health
- Kathleen M. Neuzil
- Center for Vaccine Development and Global Health, University of Maryland School of Medicine
- Lawrence Corey
- Vaccine and Infectious Disease Division, Fred Hutchinson Cancer Center
- Alexander L. Greninger
- Vaccine and Infectious Disease Division, Fred Hutchinson Cancer Center
- Pavitra Roychoudhury
- Vaccine and Infectious Disease Division, Fred Hutchinson Cancer Center
- Ollivier Hyrien
- Vaccine and Infectious Disease Division, Fred Hutchinson Cancer Center
- Peter B. Gilbert
- Vaccine and Infectious Disease Division, Fred Hutchinson Cancer Center
- DOI
- https://doi.org/10.1038/s41467-024-46536-w
- Journal volume & issue
-
Vol. 15,
no. 1
pp. 1 – 22
Abstract
Abstract 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.
