Potent human antibodies against SpA5 identified by high-throughput single-cell sequencing of phase I clinical volunteers' B cells.

Abstract

The drug resistance problem of Staphylococcus aureus needs to be solved urgently. Here, we report the rapid identification of S. aureus human antibodies by high-throughput single-cell RNA and VDJ sequencing of memory B cells derived from 64 volunteers immunized with recombinant five-component S. aureus vaccine (clinical phase I). From 676 antigen-binding IgG1⁺ clonotypes, TOP10 sequences were selected for expression and characterization, with the most potent one, Abs-9, having nanomolar affinity for the pentameric form of the specific antigen S. aureus protein A. Abs-9 also demonstrated strong prophylactic efficacy in mice injected with lethal doses of a wide range of drug-resistant S. aureus strains. Additionally, the potential epitopes were predicted and validated based on Alphafold2 and molecular docking methods. In all, this study screened for a potent strain of antibody that prevents infection with antibiotic-resistant S. aureus, providing important data to guide the design of vaccines based on antibody architecture.