| Title: |
Quantifying how single dose Ad26.COV2.S vaccine efficacy depends on Spike sequence features |
| Authors: |
Magaret, Craig A; Li, Li; deCamp, Allan C; Rolland, Morgane; Juraska, Michal; Williamson, Brian D; Ludwig, James; Molitor, Cindy; Benkeser, David; Luedtke, Alex; Simpkins, Brian; Heng, Fei; Sun, Yanqing; Carpp, Lindsay N; Bai, Hongjun; Dearlove, Bethany L; Giorgi, Elena E; Jongeneelen, Mandy; Brandenburg, Boerries; McCallum, Matthew; Bowen, John E; Veesler, David; Sadoff, Jerald; Gray, Glenda E; Roels, Sanne; Vandebosch, An; Stieh, Daniel J; Le Gars, Mathieu; Vingerhoets, Johan; Grinsztejn, Beatriz; Goepfert, Paul A; de Sousa, Leonardo Paiva; Silva, Mayara Secco Torres; Casapia, Martin; Losso, Marcelo H; Little, Susan J; Gaur, Aditya; Bekker, Linda-Gail; Garrett, Nigel; Truyers, Carla; Van Dromme, Ilse; Swann, Edith; Marovich, Mary A; Follmann, Dean; Neuzil, Kathleen M; Corey, Lawrence; Greninger, Alexander L; Roychoudhury, Pavitra; Hyrien, Ollivier; Gilbert, Peter B |
| Source: |
Nature Communications, vol 15, iss 1 |
| Publisher Information: |
eScholarship, University of California |
| Publication Year: |
2024 |
| Collection: |
University of California: eScholarship |
| Subject Terms: |
31 Biological Sciences (for-2020); 32 Biomedical and Clinical Sciences (for-2020); 3204 Immunology (for-2020); Immunization (rcdc); Vaccine Related (rcdc); Clinical Research (rcdc); Biotechnology (rcdc); Emerging Infectious Diseases (rcdc); Infectious Diseases (rcdc); Clinical Trials and Supportive Activities (rcdc); Prevention (rcdc); Coronaviruses (rcdc); 3 Good Health and Well Being (sdg); Humans (mesh); Ad26COVS1 (mesh); COVID-19 (mesh); SARS-CoV-2 (mesh); Vaccine Efficacy (mesh); Amino Acids (mesh); Antibodies; Viral (mesh); Neutralizing (mesh) |
| Time: |
2175 |
| Description: |
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 themost distant viruses. |
| Document Type: |
article in journal/newspaper |
| File Description: |
application/pdf |
| Language: |
unknown |
| Relation: |
qt3x39f2hc; https://escholarship.org/uc/item/3x39f2hc; https://escholarship.org/content/qt3x39f2hc/qt3x39f2hc.pdf |
| DOI: |
10.1038/s41467-024-46536-w |
| Availability: |
https://escholarship.org/uc/item/3x39f2hc; https://escholarship.org/content/qt3x39f2hc/qt3x39f2hc.pdf; https://doi.org/10.1038/s41467-024-46536-w |
| Rights: |
CC-BY |
| Accession Number: |
edsbas.98D14BA9 |
| Database: |
BASE |