Broadly neutralizing antibodies to SARS-related viruses can be readily induced in rhesus macaques

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.

Broadly neutralizing antibodies against sarbecoviruses generated by immunization of macaques with an AS03-adjuvanted COVID-19 vaccine

“…Some of the authors of this study previously determined two antibody structures encoded by a highly enriched germline gene, VH3-73 , in macaques ( 27 ). In the present study, we show that another VH3-73 –encoded antibody, 20A7, adopts the same binding mode (fig.…”

Characterization of cross‐reactive monoclonal antibodies against SARS‐CoV‐1 and SARS‐CoV‐2: Implication for rational design and development of pan‐sarbecovirus vaccines and neutralizing antibodies

“…Importantly, the potent bNAbs against SARS‐CoV‐1, SARS‐CoV‐2 VOCs, and SARS‐COV‐2 Omicron and its sublineages were indeed identified. For example, antibody K398.22 48 potently neutralized both SARS‐CoV‐1 and Omicron, with its IC 50 values of 32 and 6 ng/ml, respectively (Figure ). Moreover, by screening more than 1400 mAbs, broad‐spectrum neutralizing mAbs, SA58, and SA55, recognizing two nonoverlapping super‐conserved epitopes, were recently identified, with potent neutralizing activities against both SARS‐CoV‐1 (IC 50 values: 4–6 ng/ml) and Omicron and its sublineages (IC 50 values: 1–11 ng/ml) 44 (Figure 7F).…”

Extremely potent pan-sarbecovirus neutralizing antibodies generated by immunization of macaques with an AS03-adjuvanted monovalent subunit vaccine against SARS-CoV-2

“…Some of the authors of this study previously determined two antibody structures encoded by a highly enriched germline gene VH3-73 in SARS-CoV-2-immunized macaques ( 25 ). In the present study, we show that another VH3-73-encoded antibody, 20A7, adopts the same binding mode ( fig.…”