2024-08-27 カリフォルニア工科大学(Caltech)
<関連情報>
- https://www.caltech.edu/about/news/multipurpose-vaccine-shows-new-promise-in-the-presence-of-pre-existing-immunity
- https://www.cell.com/cell/fulltext/S0092-8674(24)00846-8
モザイクサルベコウイルスナノ粒子はワクチン接種前の動物で交差反応性応答を誘発する Mosaic sarbecovirus nanoparticles elicit cross-reactive responses in pre-vaccinated animals
Alexander A. Cohen,Jennifer R. Keeffe,Ariën Schiepers,…,Deborah H. Fuller,Gabriel D. Victora,Pamela J. Bjorkman
Cell Published:August 26, 2024
DOI:https://doi.org/10.1016/j.cell.2024.07.052
Graphical abstract
Highlights
- Pan-sarbecovirus vaccine evaluated in pre-vaccinated monkeys and mice
- Mosaic nanoparticles elicited broad antibody responses after COVID-19 vaccinations
- Epitope and molecular fate mapping revealed cross-reactive recall responses
- Original antigenic sin did not diminish immune responses to a mosaic vaccine
Summary
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.
