Mosaic RBD Nanoparticles Protect Against Challenge by Diverse Sarbecoviruses in Animal Models

Overview

Journal Science

Specialty Science

Date 2022 Jul 20

PMID 35857620

Authors

Alexander A Cohen

Neeltje van Doremalen

Allison J Greaney

Hanne Andersen

Ankur Sharma

Tyler N Starr

Jennifer R Keeffe

Chengcheng Fan

Jonathan E Schulz

Priyanthi N P Gnanapragasam

Leesa M Kakutani

Anthony P West Jr

Greg Saturday

Yu E Lee

Han Gao

Claudia A Jette

Mark G Lewis

Tiong K Tan

Alain R Townsend

Jesse D Bloom

Vincent J Munster

Pamela J Bjorkman

Affiliations

Soon will be listed here.

Abstract

To combat future severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) variants and spillovers of SARS-like betacoronaviruses (sarbecoviruses) threatening global health, we designed mosaic nanoparticles that present randomly arranged sarbecovirus spike receptor-binding domains (RBDs) to elicit antibodies against epitopes that are conserved and relatively occluded rather than variable, immunodominant, and exposed. We compared immune responses elicited by mosaic-8 (SARS-CoV-2 and seven animal sarbecoviruses) and homotypic (only SARS-CoV-2) RBD nanoparticles in mice and macaques and observed stronger responses elicited by mosaic-8 to mismatched (not on nanoparticles) strains, including SARS-CoV and animal sarbecoviruses. Mosaic-8 immunization showed equivalent neutralization of SARS-CoV-2 variants, including Omicrons, and protected from SARS-CoV-2 and SARS-CoV challenges, whereas homotypic SARS-CoV-2 immunization protected only from SARS-CoV-2 challenge. Epitope mapping demonstrated increased targeting of conserved epitopes after mosaic-8 immunization. Together, these results suggest that mosaic-8 RBD nanoparticles could protect against SARS-CoV-2 variants and future sarbecovirus spillovers.

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