A Novel Human IgA Monoclonal Antibody Protects against Tuberculosis

Abstract

Abs have been shown to be protective in passive immunotherapy of tuberculous infection using mouse experimental models. In this study, we report on the properties of a novel human IgA1, constructed using a single-chain variable fragment clone (2E9), selected from an Ab phage library. The purified Ab monomer revealed high binding affinities for the mycobacterial α-crystallin Ag and for the human FcαRI (CD89) IgA receptor. Intranasal inoculations with 2E9IgA1 and recombinant mouse IFN-γ significantly inhibited pulmonary H37Rv infection in mice transgenic for human CD89 but not in CD89-negative littermate controls, suggesting that binding to CD89 was necessary for the IgA-imparted passive protection. 2E9IgA1 added to human whole-blood or monocyte cultures inhibited luciferase-tagged H37Rv infection although not for all tested blood donors. Inhibition by 2E9IgA1 was synergistic with human rIFN-γ in cultures of purified human monocytes but not in whole-blood cultures. The demonstration of the mandatory role of FcαRI (CD89) for human IgA-mediated protection is important for understanding of the mechanisms involved and also for translation of this approach toward development of passive immunotherapy of tuberculosis.

Mucosal delivery of antigen‐coated nanoparticles to lungs confers protective immunity against tuberculosis infection in mice

“…However, we and others have shown in previous studies that passive transfer of monoclonal antibodies can reduce infection with MTB in mice [9,[22][23][24][25][26][27][28], although it is unclear if active immunisation could induce similar levels of antibodies and of the same epitope specificity. Therefore, further work is required to fully characterise the role of Ab responses induced by the Nano-AH vaccine, in protection against MTB infection.…”

B lymphocytes that migrate to tuberculous pleural fluid via the SDF‐1/CXCR4 axis actively respond to antigens specific for Mycobacterium tuberculosis

“…However, it is worth noting that any successful, novel vaccine strategy against TB will have to properly invoke both humoral and cellular immunity, given that these responses are the two critical arms of adaptive immunity and always collaborate to repel infectious pathogens [9]. Numerous murine studies have shown that B cells and antibodies have pleiotropic activities and display previously underappreciated roles during M. tuberculosis infection [10][11][12]. In contrast to the murine studies, there are limited data regarding any phenotypic and functional characterization of the B-cell compartment in TB patients, especially in patients with tuberculous pleuritis (TP), who are known to have a relatively strong immune defense against M. tuberculosis at the local site of disease [13].…”

Latently and uninfected healthcare workers exposed to TB make protective antibodies against Mycobacterium tuberculosis

“…Furthermore, as an intracellular pathogen, it has been argued that Mtb would not be within the therapeutic reach of antibodies. Nonetheless, multiple studies have shown the efficacy of mAbs in ameliorating murine models of TB infection (6)(7)(8)(9)(10)(11)(12), and antibodymediated immunity to several intracellular pathogens, including Cryptococcus neoformans and typhoid Salmonella, has been documented (13), raising the possibility that antibody-mediated immunity may also exist for TB. Pooled Igs from human donors have been shown to protect mice against Mtb (14), but it was not known if this was caused by a generalized immunomodulatory effect (15) targeting the inflammatory component of the disease or whether protective antibodies directly targeting critical mycobacterial antigens could be isolated from individuals.…”