Affinity maturation endows potent activity onto class 6 SARS-CoV-2 broadly neutralizing antibodies.

ABSTRACT: The emergence of SARS-CoV-2 variants of concern (VOCs) has greatly diminished the neutralizing activity of previously FDA-approved monoclonal antibodies (mAbs), including that of antibody cocktails and of first-generation broadly neutralizing antibodies such as S309 (Sotrovimab). In contrast, antibodies targeting cryptic conformational epitopes of the receptor binding domain (RBD) have demonstrated broad activity against emerging variants, but exert only moderate neutralizing activity, which has so far hindered clinical development. Here, we utilize in vitro display technology to identify and affinity-mature antibodies targeting the cryptic class 6 epitope, accessible only in the "up" conformation of the SARS-CoV-2 spike trimer. Increasing antibody affinity into the low picomolar range end

SUBMITTER: Mazigi O 

PROVIDER: S-EPMC11725916 | biostudies-literature | 2025 Jan

REPOSITORIES: biostudies-literature