Antibodies as clinical tools for tuberculosis

Sophie McIntyre; Jeffrey Warner; Catherine Rush; Hillary A Vanderven

doi:10.3389/fimmu.2023.1278947

Antibodies as clinical tools for tuberculosis

Front Immunol. 2023 Dec 14:14:1278947. doi: 10.3389/fimmu.2023.1278947. eCollection 2023.

Authors

Sophie McIntyre^{1

2}, Jeffrey Warner^{1

2}, Catherine Rush^{1

2}, Hillary A Vanderven^{1

2

3}

Affiliations

¹ Biomedical Sciences and Molecular Biology, College of Public Health, Medical and Veterinary Sciences, James Cook University, Douglas, QLD, Australia.
² Australian Institute of Tropical Health and Medicine, James Cook University, Douglas, QLD, Australia.
³ Department of Microbiology and Immunology, Peter Doherty Institute for Infection and Immunity, University of Melbourne, Parkville, VIC, Australia.

Abstract

Tuberculosis (TB) is a leading cause of morbidity and mortality worldwide. Global research efforts to improve TB control are hindered by insufficient understanding of the role that antibodies play in protective immunity and pathogenesis. This impacts knowledge of rational and optimal vaccine design, appropriate diagnostic biomarkers, and development of therapeutics. Traditional approaches for the prevention and diagnosis of TB may be less efficacious in high prevalence, remote, and resource-poor settings. An improved understanding of the immune response to the causative agent of TB, Mycobacterium tuberculosis (Mtb), will be crucial for developing better vaccines, therapeutics, and diagnostics. While memory CD4+ T cells and cells and cytokine interferon gamma (IFN-g) have been the main identified correlates of protection in TB, mounting evidence suggests that other types of immunity may also have important roles. TB serology has identified antibodies and functional characteristics that may help diagnose Mtb infection and distinguish between different TB disease states. To date, no serological tests meet the World Health Organization (WHO) requirements for TB diagnosis, but multiplex assays show promise for improving the sensitivity and specificity of TB serodiagnosis. Monoclonal antibody (mAb) therapies and serum passive infusion studies in murine models of TB have also demonstrated some protective outcomes. However, animal models that better reflect the human immune response to Mtb are necessary to fully assess the clinical utility of antibody-based TB prophylactics and therapeutics. Candidate TB vaccines are not designed to elicit an Mtb-specific antibody response, but evidence suggests BCG and novel TB vaccines may induce protective Mtb antibodies. The potential of the humoral immune response in TB monitoring and control is being investigated and these studies provide important insight into the functional role of antibody-mediated immunity against TB. In this review, we describe the current state of development of antibody-based clinical tools for TB, with a focus on diagnostic, therapeutic, and vaccine-based applications.

Keywords: antibodies; humoral immunity; immunotherapy; monoclonal antibodies; mycobacteria; serodiagnostics; tuberculosis; vaccines.

Publication types

Review
Research Support, Non-U.S. Gov't

MeSH terms

Animals
Antibodies
Cytokines
Humans
Interferon-gamma
Mice
Mycobacterium tuberculosis*
Tuberculosis Vaccines*
Tuberculosis*

Substances

Tuberculosis Vaccines
Cytokines
Interferon-gamma
Antibodies

Grants and funding

The author(s) declare financial support was received for the research, authorship, and/or publication of this article. The publication of this review was supported in part by a James Cook University Higher Degree by Research Enhancement Scheme grant.