Broadly neutralizing antibodies to SARS-related viruses can be readily induced in rhesus macaques
Name
scitranslmed.abl9605.pdf
Description
Published version
Size
8.21 MB
Format
Adobe PDF
Checksum (MD5)
9243233500c6974ae40bea0b453deee4
Author(s)
Irvine, Darrell
Date Issued
2022
Journal
Science Translational Medicine
Publisher
American Association for the Advancement of Science (AAAS)
Citation
Irvine, Darrell. 2022. "Broadly neutralizing antibodies to SARS-related viruses can be readily induced in rhesus macaques." Science Translational Medicine, 14 (657).
Version
Final published version
Abstract
To prepare for future coronavirus (CoV) pandemics, it is desirable to generate vaccines capable of eliciting broadly neutralizing antibody responses to CoVs. Here, we show that immunization of macaques with SARS-CoV-2 spike (S) protein with a two-shot protocol generated potent serum receptor binding domain cross-neutralizing antibody responses to both SARS-CoV-2 and SARS-CoV-1. Furthermore, responses were equally effective against most SARS-CoV-2 variants of concern (VOCs) and some were highly effective against Omicron. This result contrasts with human infection or many two-shot vaccination protocols where responses were typically more SARS-CoV-2 specific and where VOCs were less well neutralized. Structural studies showed that cloned macaque neutralizing antibodies, particularly using a given heavy chain germline gene, recognized a relatively conserved region proximal to the angiotensin converting enzyme 2 receptor binding site (RBS), whereas many frequently elicited human neutralizing antibodies targeted more variable epitopes overlapping the RBS. B cell repertoire differences between humans and macaques appeared to influence the vaccine response. The macaque neutralizing antibodies identified a pan-SARS–related virus epitope region less well targeted by human antibodies that could be exploited in rational vaccine design.
MIT Department
Massachusetts Institute of Technology. Department of Biological Engineering
Terms of Use
Creative Commons Attribution 4.0 International license
Persistent DSpace Link
DOI of Published Version
https://doi.org/10.1126/SCITRANSLMED.ABL9605
