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

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Krishnananthasivam, Shivankari  ORCID logo
Li, Hao 
Bouzeyen, Rania 
Shunmuganathan, Bhuvaneshwari 
Purushotorman, Kiren  ORCID logo

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.

3207 Medical Microbiology, 32 Biomedical and Clinical Sciences, 3204 Immunology, Clinical Research, Emerging Infectious Diseases, Infectious Diseases, Orphan Drug, Biotechnology, Rare Diseases, Immunization, Prevention, HIV/AIDS, Vaccine Related, Biodefense, Tuberculosis, 2.1 Biological and endogenous factors, 2 Aetiology, Infection, 3 Good Health and Well Being
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NPJ Vaccines
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Springer Science and Business Media LLC
Bill and Melinda Gates Foundation (571-000-030-720, INV-038660)
Bill & Melinda Gates Foundation (INV-038660)
National Natural Science Foundation of China (81661128044)
Wellcome Trust (207487/C/17/Z)