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

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...

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Bibliographic Details
Published in:npj vaccines 2023-08, Vol.8 (1), p.127-12, Article 127
Main Authors: Krishnananthasivam, Shivankari, Li, Hao, Bouzeyen, Rania, Shunmuganathan, Bhuvaneshwari, Purushotorman, Kiren, Liao, Xinlei, Du, Fengjiao, Friis, Claudia Guldager Kring, Crawshay-Williams, Felicity, Boon, Low Heng, Xinlei, Qian, Chan, Conrad En Zuo, Sobota, Radoslaw, Kozma, Mary, Barcelli, Valeria, Wang, Guirong, Huang, Hairong, Floto, Andreas, Bifani, Pablo, Javid, Babak, MacAry, Paul A.
Format: Article
Language:English
Subjects:
692/53
692/699/255/1856
Antigens
Asymptomatic
Biomedical and Life Sciences
Biomedicine
Cells
Health care
Infections
Infectious Diseases
Laboratories
Lymphocytes
Medical Microbiology
Monoclonal antibodies
Occupational exposure
Pathogens
Public Health
Tuberculosis
Vaccine
Vaccines
Virology
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Summary: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.
ISSN:2059-0105
2059-0105
DOI:10.1038/s41541-023-00710-1