An anti-LpqH human monoclonal antibody from an asymptomatic individual mediates protection against Mycobacterium tuberculosis

作者：Shivankari Krishnananthasivam, Hao Li, Rania Bouzeyen, Bhuvaneshwari D O Shunmuganathan, Kiren Purushotorman, Xinlei Liao, Fengjiao Du, Claudia Guldager Kring Friis, Felicity Crawshay‐Williams, Low Heng Boon, Qian Xinlei, Conrad En Zuo Chan, Radoslaw M. Sobota, Mary Kozma, Valeria Barcelli, Guirong Wang, Hairong Huang, Andreas Floto, Pablo Bifani, Babak Javid, Paul A. MacAry · 发表于：npj Vaccines · 年份：2023 · DOI：10.1038/s41541-023-00710-1 · 被引用次数：23 · 研究领域：Tuberculosis Research and Epidemiology、Mycobacterium research and diagnosis、Monoclonal and Polyclonal Antibodies Research

Tuberculosis (TB) is an airborne disease caused by Mycobacterium tuberculosis (Mtb). Whilst a functional role for humoral immunity in Mtb protection remains poorly defined, previous studies have suggested that antibodies can contribute towards host defense. Thus, identifying the critical components in the antibody repertoires from immune, chronically exposed, healthy individuals represents an approach for identifying new determinants for natural protection. In this study, we performed a thorough analysis of the IgG/IgA memory B cell repertoire from occupationally exposed, immune volunteers. We detail the identification and selection of a human monoclonal antibody that exhibits protective activity in vivo and show that it targets a virulence factor LpqH. Intriguingly, protection in both human ex vivo and murine challenge experiments was isotype dependent, with most robust protection being mediated via IgG2 and IgA. These data have important implications for our understanding of natural mucosal immunity for Mtb and highlight a new target for future vaccine development.