Post by Nadica (She/Her) on Jul 31, 2024 0:37:23 GMT
Broad sarbecovirus neutralization by combined memory B cell antibodies to ancestral SARS-CoV-2 - Published June 22, 2024
Highlights
•Cv2.3194 is a resilient class 1 RBD SARS-CoV-2 neutralizer active up to BA.2.86
•Cv2.3132, a broadly sarbecovirus neutralizer, targets the HR2 membrane proximal region
•Combined Cv2.3132 and Cv2.3194 cooperate to neutralize SARS-CoV-2 variants in vitro
•Cv2.3132 and Cv2.3194 provide protection against SARS-CoV-2 infection in mouse models
Summary
Antibodies play a pivotal role in protecting from SARS-CoV-2 infection, but their efficacy is challenged by the continuous emergence of viral variants. In this study, we describe two broadly neutralizing antibodies cloned from the memory B cells of a single convalescent individual after infection with ancestral SARS-CoV-2. Cv2.3194, a resilient class 1 anti-RBD antibody, remains active against Omicron sub-variants up to BA.2.86. Cv2.3132, a near pan-Sarbecovirus neutralizer, targets the heptad repeat 2 membrane proximal region. When combined, Cv2.3194 and Cv2.3132 form a complementary SARS-CoV-2 neutralizing antibody cocktail exhibiting a local dose-dependent synergy. Thus, remarkably robust neutralizing memory B cell antibodies elicited in response to ancestral SARS-CoV-2 infection can withstand viral evolution and immune escape. The cooperative effect of such antibody combination may confer a certain level of protection against the latest SARS-CoV-2 variants.
Graphical abstract
Highlights
•Cv2.3194 is a resilient class 1 RBD SARS-CoV-2 neutralizer active up to BA.2.86
•Cv2.3132, a broadly sarbecovirus neutralizer, targets the HR2 membrane proximal region
•Combined Cv2.3132 and Cv2.3194 cooperate to neutralize SARS-CoV-2 variants in vitro
•Cv2.3132 and Cv2.3194 provide protection against SARS-CoV-2 infection in mouse models
Summary
Antibodies play a pivotal role in protecting from SARS-CoV-2 infection, but their efficacy is challenged by the continuous emergence of viral variants. In this study, we describe two broadly neutralizing antibodies cloned from the memory B cells of a single convalescent individual after infection with ancestral SARS-CoV-2. Cv2.3194, a resilient class 1 anti-RBD antibody, remains active against Omicron sub-variants up to BA.2.86. Cv2.3132, a near pan-Sarbecovirus neutralizer, targets the heptad repeat 2 membrane proximal region. When combined, Cv2.3194 and Cv2.3132 form a complementary SARS-CoV-2 neutralizing antibody cocktail exhibiting a local dose-dependent synergy. Thus, remarkably robust neutralizing memory B cell antibodies elicited in response to ancestral SARS-CoV-2 infection can withstand viral evolution and immune escape. The cooperative effect of such antibody combination may confer a certain level of protection against the latest SARS-CoV-2 variants.
Graphical abstract