Human monoclonal antibodies against Staphylococcus aureus A protein identified by high-throughput single-cell sequencing of phase I clinical volunteers' B cells

• Published in: Clinical immunology (Orlando, Fla.) Vol. 257; p. 109843
• Main Authors: Wang, WenHao, Gu, YaRu, Ou, YangXue, Zhou, JinRui, Liu, BiXia, Zuo, HouYi, Du, YeXiang, Wang, Ying, Tang, TengQian, Zou, QuanMing, Zuo, QianFei
• Format: Journal Article
• Language: English
• Published: United States Elsevier Inc 01.12.2023
• Subjects: Antibodies, Bacterial; Antibodies, Monoclonal; Human monoclonal antibody; Humans; Immunoglobulin G; Methicillin-Resistant Staphylococcus aureus - genetics; Single-Cell Sequencing; Staphylococcal Infections; Staphylococcus aureus; Staphylococcus aureus - genetics; Staphylococcus aureus - metabolism; Staphylococcus aureus protein a; Staphylococcus aureus protein a; Single-Cell Sequencing; Staphylococcus aureus; Human monoclonal antibody
• ISSN: 1521-6616; 1521-7035; 1521-7035
• DOI: 10.1016/j.clim.2023.109843

Methicillin-resistant Staphylococcus aureus, poses a significant threat through infections in both community and hospital settings. To address this challenge, we conducted a phase I clinical trial study involving a recombinant Staphylococcus aureus vaccine. Utilizing peripheral blood lymphocytes from 64 subjects, we isolated antigen-specific memory B cells for subsequent single-cell sequencing. Among the 676 identified antigen-binding IgG1+ clones, we selected the top 10 antibody strains for construction within expression vectors. Successful expression and purification of these monoclonal antibodies led to the discovery of a highly expressed human antibody, designated as IgG-6. This antibody specifically targets the pentameric form of the Staphylococcus aureus protein A (SpA5). In vivo assessments revealed that IgG-6 provided prophylactic protection against MRSA252 infection. This study underscores the potential of human antibodies as an innovative strategy against Staphylococcus aureus infections, offering a promising avenue for further research and clinical development. •676 IgG1+ antigen-binding clonotypes were identified by high-throughput scRNA/VDJ-seq.•IgG-6 was screened from PBMC separated from 64 phase I clinical volunteers.•IgG-6 provided prophylactic protection against MRSA252 infection.