Updates on antibody functions in Mycobacterium tuberculosis infection and their relevance for developing a vaccine against tuberculosis

Abstract

A more effective vaccine to control tuberculosis (TB), a major global public health problem, is urgently needed. Current vaccine candidates focus predominantly on eliciting cell-mediated immunity but other arms of the immune system also contribute to protection against TB. We review here recent studies that enhance our current knowledge of antibody-mediated functions against Mycobacterium tuberculosis. These findings, which contribute to the increasing evidence that antibodies have a protective role against TB, include demonstrations that firstly distinct human antibody Fc glycosylation patterns, found in latent M. tuberculosis infection but not in active TB, influence the efficacy of the host to control M. tuberculosis infection, secondly antibody isotype influences human antibody functions, and thirdly that antibodies targeting M. tuberculosis surface antigens are protective. We discuss these findings in the context of TB vaccine development and highlight the need for further research on antibody-mediated immunity in M. tuberculosis infection.

Figure 1

Conceptual view of Ab-mediated protection induced by a TB vaccine. (A) The ideal vaccine would prevent M. tuberculosis infection in the uninfected and development of disease in the already infected individual through mucosal airway and/or systemic vaccination. (B) Induction of protective M. tuberculosis antigen-specific antibody responses with potential enhancement of cell-mediated responses. (C) Illustration of several antibody-mediated functions against M. tuberculosis, including opsonization, FcR-mediated phagocytosis and intracellular growth reduction, influence on the host’s inflammatory response, direct effects on the M. tuberculosis physiology, and influence of immune complexes on the host and host cells.