Mosaic sarbecovirus nanoparticles elicit cross-reactive responses in pre-vaccinated animals
Immunization with mosaic-8b (nanoparticles presenting 8 SARS-like betacoronavirus [sarbecovirus] receptor-binding domains [RBDs]) elicits more broadly cross-reactive antibodies than homotypic SARS-CoV-2 RBD-only nanoparticles and protects against sarbecoviruses. To investigate original antigenic sin (OAS) effects on mosaic-8b efficacy, we evaluated the effects of prior COVID-19 vaccinations in non-human primates and mice on anti-sarbecovirus responses elicited by mosaic-8b, admix-8b (8 homotypics), or homotypic SARS-CoV-2 immunizations, finding the greatest cross-reactivity for mosaic-8b. As demonstrated by molecular fate mapping, in which antibodies from specific cohorts of B cells are differentially detected, B cells primed by WA1 spike mRNA-LNP dominated antibody responses after RBD-nanoparticle boosting. While mosaic-8b- and homotypic-nanoparticles boosted cross-reactive antibodies, de novo antibodies were predominantly induced by mosaic-8b, and these were specific for variant RBDs with increased identity to RBDs on mosaic-8b. These results inform OAS mechanisms and support using mosaic-8b to protect COVID-19-vaccinated/infected humans against as-yet-unknown SARS-CoV-2 variants and animal sarbecoviruses with human spillover potential.
Authors
- Chengcheng Fan (ORCID: https://orcid.org/0000-0003-4213-5758)
- Sandra Dross (ORCID: https://orcid.org/0000-0003-1013-6828)
- Gabriel D. Victora (ORCID: https://orcid.org/0000-0001-8807-348X)
- Alexander A. Cohen (ORCID: https://orcid.org/0000-0002-2818-656X)
- Jesse H. Erasmus (ORCID: https://orcid.org/0000-0003-1612-2697)
- Arlene I. Ramsingh
- Leonardo Magneschi (ORCID: https://orcid.org/0000-0002-2189-2314)
- Annie V. Rorick (ORCID: https://orcid.org/0009-0003-1801-6940)
- Paulo J.C. Lin
- Priyanthi N.P. Gnanapragasam
- Ian Fotheringham
- Rita Cruz (ORCID: https://orcid.org/0000-0002-6176-7892)
- Cristina Serrano-Amatriain
- Scott Baxter
- Han Gao (ORCID: https://orcid.org/0000-0001-7240-5769)
- Ellis Robb
- Norbert Pardi (ORCID: https://orcid.org/0000-0003-1008-6242)
- Pamela J. Björkman (ORCID: https://orcid.org/0000-0002-2277-3990)
- Janice D. Pata (ORCID: https://orcid.org/0000-0001-5999-5442)
- DEBORAH HEYDENBURG FULLER (ORCID: https://orcid.org/0000-0001-7315-2441)
- Allison J. Greaney (ORCID: https://orcid.org/0000-0001-7202-3349)
- Jennifer R. Keeffe (ORCID: https://orcid.org/0000-0002-5317-6398)
- Ariën Schiepers (ORCID: https://orcid.org/0000-0002-5185-364X)
- Martina Quintanar‐Audelo
- Anthony P. West (ORCID: https://orcid.org/0000-0003-4213-5184)
- Hiromi Muramatsu (ORCID: https://orcid.org/0000-0003-1544-1493)
Institutions
- California Institute of Technology (US)
- New York State Department of Health (US)
- Wadsworth Center (US)
- University of Washington (US)
- University at Albany, State University of New York (US)
- Ingenza (United Kingdom) (GB)
- Acuitas Therapeutics (Canada) (CA)
- University of Pennsylvania (US)
- Rockefeller University (US)
Publication Details
- Journal
- Cell
- Published
- 2024-08-26
- DOI
- https://doi.org/10.1016/j.cell.2024.07.052
- Citations
- 36
- Primary Topic
- SARS-CoV-2 and COVID-19 Research
- Type
- article
- Field-Weighted Citation Impact
- 14.00
Funders
- Bill and Melinda Gates Foundation