Abstract: Here, the inventors report that natural WT SARS-CoV-2 infection induces memory B cells expressing potently neutralizing antibodies against VOCs. Moreover, natural WT infection largely induced antibodies against spike epitopes outside of the RBD, most of which were non-neutralizing against WT and VOCs. Additionally. RBD-binding antibodies could be categorized into 3 distinct classes based on their binding profiles against RBD mutant constructs. The inventors identified VOC-neutralizing antibodies against three distinct regions of the spike protein, including the two epitopes on the RBD and one epitope in the NTD. Together, this study identifies that natural WT infection induces memory B cells that can produce neutralizing antibodies against recent SARS-CoV-2 VOCs and have the potential to be recalled by vaccination.

Abstract: To address the need in the art, the inventors have comprehensively characterized the SARS-CoV-2-specific B cell repertoire in convalescent COVID-19 patients and generated mAbs against the spike, ORF8, and NP proteins. Together, the inventors' data reveal key insight into antigen specificity and B cell subset distribution upon SARS-CoV-2 infection in the context of age, sex, and disease severity. Aspects of the disclosure relate to novel antibody and antigen binding fragments. Further aspects relate to polypeptides comprising the antigen binding fragment(s) of the disclosure, and compositions comprising the polypeptides, antibodies, and/or antigen binding fragments of the disclosure. Also described are nucleic acids encoding an antibody or antigen binding fragment of the disclosure.