The role of antibodies in tuberculosis diagnosis, prophylaxis and therapy: a review from the ESGMYC study group

Abstract

Tuberculosis (TB) is still responsible for the deaths of >1 million people yearly worldwide, and therefore its correct diagnosis is one of the key components of any TB eradication programme. However, current TB diagnostic tests have many limitations, and improved diagnostic accuracy is urgently needed. To improve the diagnostic performance of traditional serology, a combination of different Mycobacterium tuberculosis (MTB) antigens and different antibody isotypes has been suggested, with some showing promising performance for the diagnosis of active TB. Given the incomplete protection conferred by bacille Calmette–Guérin (BCG) vaccination against adult pulmonary TB, efforts to discover novel TB vaccines are ongoing. Efficacy studies from advanced TB vaccines designed to stimulate cell-mediated immunity failed to show protection, suggesting that they may not be sufficient and warranting the need for other types of immunity. The role of antibodies as tools for TB therapy, TB diagnosis and TB vaccine design is discussed. Finally, we propose that the inclusion of antibody-based TB vaccines in current clinical trials may be advisable to improve protection.

Discovery of Novel Transketolase Epitopes and the Development of IgG-Based Tuberculosis Serodiagnostics

“…There is a need for a new conceptual approach with which to understand the complex host immune response to mycobacteria, including the mechanisms of humoral immunity ( 8 , 23 ). The role of cell-mediated immunity in the defense against TB is well-known, but the role of antibodies in providing protection and their utilization as a diagnostic tool has not been well-established ( 9 , 24 ).…”

“…The target product profiles (TPPs) issued by the WHO that define nonsputum-based, rapid biomarker performance as a triage test recommend a sensitivity of >95% and a specificity of >80% to screen patients with suspected TB disease and to reduce the population that requires confirmatory tests ( 5 , 8 ). Our data indicate that our TKT-specific ELISAs fulfill these criteria and are suitable for this purpose.…”

“…Efficacy studies from advanced TB vaccines that are designed to stimulate cell-mediated immunity failed to show consistent protection, warranting the need to harness other types of immunity, including antibody and B cell responses ( 8 , 9 , 37 ). One important consideration is whether TKTμ, M.tb TKT1, and M.tb TKT3 can serve as vaccine candidates.…”

“…Current commercially available antibody-based TB tests show poor sensitivity and specificity, and none can distinguish active TB from LTBI ( 6 ). Due to the lack of precision, the WHO does not endorse the routine application of the current commercial serological tests for TB diagnosis ( 7 , 8 ). The serological diagnosis of tuberculosis has been challenging, partly due to the large M.tb proteome, the even larger antigenic epitopes ( 4 ), and the heterogeneity across humans in their immunoglobulin G (IgG) responses to tuberculosis ( 9 ).…”

Mouse Models for Mycobacterium tuberculosis Pathogenesis: Show and Do Not Tell

“…Research with mice could also be implemented in revealing the role of antibodies in the tuberculosis course, but also in tuberculosis diagnosis and treatment. Currently, new strategies in diagnosis based on detection and quantification of antibodies in blood samples, using them as biomarkers of the disease, as well as therapeutic strategies based on administration of antibodies, are gaining popularity [ 252 ]. Proof of concept assays could be performed using the different mice models to explore the antibody patterns and responses generated under M. tuberculosis infections, from active stage (C3HeB/FeJ) to latent stage (C57BL/6).…”