An Anti-LpqH Human Monoclonal Antibody from an Asymptomatic Individual Mediates Protection Against Mycobacterium Tuberculosis

Overview

Journal NPJ Vaccines

Date 2023 Aug 25

PMID 37626082

Authors

Shivankari Krishnananthasivam

Hao Li

Rania Bouzeyen

Bhuvaneshwari Shunmuganathan

Kiren Purushotorman

Xinlei Liao

Fengjiao Du

Claudia Guldager Kring Friis

Felicity Crawshay-Williams

Low Heng Boon

Qian Xinlei

Conrad En Zuo Chan

Radoslaw Sobota

Mary Kozma

Valeria Barcelli

Guirong Wang

Hairong Huang

Andreas Floto

Pablo Bifani

Babak Javid

Paul A Macary

Affiliations

Soon will be listed here.

Abstract

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.

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