Tweet
Sci Transl Med
. 2022 Aug 10;14(657):eabl9605.
doi: 10.1126/scitranslmed.abl9605. Epub 2022 Aug 10.
Broadly neutralizing antibodies to SARS-related viruses can be readily induced in rhesus macaques
Wan-Ting He 1 2 3 , Meng Yuan 4 , Sean Callaghan 1 2 3 , Rami Musharrafieh 1 2 3 , Ge Song 1 2 3 , Murillo Silva 3 5 , Nathan Beutler 1 , Wen-Hsin Lee 4 , Peter Yong 1 2 3 , Jonathan L Torres 4 , Mariane Melo 3 5 , Panpan Zhou 1 2 3 , Fangzhu Zhao 1 2 3 , Xueyong Zhu 4 , Linghang Peng 1 , Deli Huang 1 , Fabio Anzanello 1 2 3 , James Ricketts 1 , Mara Parren 1 , Elijah Garcia 1 , Melissa Ferguson 6 , William Rinaldi 6 , Stephen A Rawlings 7 , David Nemazee 1 , Davey M Smith 7 , Bryan Briney 1 2 3 , Yana Safonova 8 , Thomas F Rogers 1 7 , Jennifer M Dan 7 9 , Zeli Zhang 9 , Daniela Weiskopf 9 , Alessandro Sette 7 9 , Shane Crotty 3 7 9 , Darrell J Irvine 3 5 10 11 12 , Andrew B Ward 2 3 4 , Ian A Wilson 2 3 4 13 , Dennis R Burton 1 2 3 12 , Raiees Andrabi 1 2 3
Affiliations
- PMID: 35947674
- DOI: 10.1126/scitranslmed.abl9605
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.