Skip to main page content
U.S. flag

An official website of the United States government

Dot gov

The .gov means it’s official.
Federal government websites often end in .gov or .mil. Before sharing sensitive information, make sure you’re on a federal government site.

Https

The site is secure.
The https:// ensures that you are connecting to the official website and that any information you provide is encrypted and transmitted securely.

Access keys NCBI Homepage MyNCBI Homepage Main Content Main Navigation
Review
. 2023 Dec 14:14:1278947.
doi: 10.3389/fimmu.2023.1278947. eCollection 2023.

Antibodies as clinical tools for tuberculosis

Sophie McIntyre  1   2 , Jeffrey Warner  1   2 , Catherine Rush  1   2 , Hillary A Vanderven  1   2   3
Affiliations
Review

Antibodies as clinical tools for tuberculosis

Sophie McIntyre et al. Front Immunol. .

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.

PubMed Disclaimer

Conflict of interest statement

The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.

Figures

Figure 1
Figure 1
An overview of adaptive immunity to Mtb infection, and the progression of TB disease presentations. Protective cell-mediated immunity against Mtb is well established, and primarily involves CD4+ T cells producing inflammatory cytokines (such as IFN-γ and TNF-α) which activate the antimicrobial functions of Mtb-infected macrophages (10, 11). Conversely, antibody-mediated immunity has a less clear role in Mtb infection, although a growing body of evidence supports a protective association between Mtb-specific antibodies and TB disease outcomes (–16). While the two branches of adaptive immunity have long been studied separately in TB, they are interconnected (17) and multiple independent studies suggest that cell- and antibody-mediated immunity are working cooperatively to protect against Mtb infection, inhibit Mtb growth and reduce disseminated TB disease (, –20). Created with BioRender.com.
Figure 2
Figure 2
Potential functions of antibodies against Mtb. Antibodies may have an array of functions in the immune response against Mtb infection. The most well-known of these is neutralization of extracellular Mtb and secreted products via the antibody fragment antigen-binding (Fab) domain. Binding of antibody to Mtb may block entry of Mtb into host cells, aid in intracellular killing or control of replication, enhance phagocytosis by opsonizing Mtb, prevent the actions of secreted proteins and help prevent dissemination from the lungs (–38). The fragment crystallizable (Fc) region of Mtb antibodies may also play a role in the immune response to Mtb. Fc-mediated antibody functions including antibody-dependent phagocytosis (ADP), antibody-dependent complement activation (ADCA), antibody-dependent cellular cytotoxicity (ADCC) and inflammasome activation may occur during Mtb infection (12, 13, 39, 40). Possible interactions with cell-mediated immunity, including enhancement of T-cell responses in the presence of specific antibodies, have been reported (14, 41). However, the precise mechanisms underlying some of the proposed Mtb antibody functions are not known or poorly defined in Mtb infection. Created with BioRender.com.
Figure 3
Figure 3
Outline of current research pathways and progress towards use of Mtb antibodies in a clinical setting. Created with BioRender.com.
See this image and copyright information in PMC

References

    1. Sanduzzi Zamparelli S, Mormile M, Sanduzzi Zamparelli A, Guarino A, Parrella R, Bocchino M. Clinical impact of COVID-19 on tuberculosis. Infez Med (2022) 30(4):495–500. doi: 10.53854/liim-3004-3 - DOI - PMC - PubMed
    1. World Health Organization . Global tuberculosis report 2022. 2 ed Vol. 2022. . Geneva: World Health Organization; (2022).
    1. Pai M, Behr MA, Dowdy D, Dheda K, Divangahi M, Boehme CC, et al. . Tuberculosis. Nat Rev Dis Primers (2016) 2(1):16076. doi: 10.1038/nrdp.2016.76 - DOI - PubMed
    1. Middleton AM, Chadwick MV, Nicholson AG, Dewar A, Groger RK, Brown EJ, et al. . Interaction of mycobacterium tuberculosis with human respiratory mucosa. Tuberculosis (Edinb) (2002) 82(2):69–78. doi: 10.1054/tube.2002.0324 - DOI - PubMed
    1. Gopalaswamy R, Dusthackeer VNA, Kannayan S, Subbian S. Extrapulmonary tuberculosis—an update on the diagnosis, treatment and drug resistance. J Respir (2021) 1(2):141–64. doi: 10.3390/jor1020015 - DOI

Publication types