A mycobacterial lipoarabinomannan specific monoclonal antibody and its F(ab′)2 fragment prolong survival of mice infected withMycobacterium tuberculosis

Abstract

SUMMARYLipoarabinomannan (LAM) is a major structural carbohydrate antigen of the outer surface of Mycobacterium tuberculosis . High antibody titres against LAM are often seen in active tuberculosis (TB). The role of such LAM-specific antibodies in the immune response against TB is unknown. Here we have investigated a monoclonal antibody (MoAb) SMITB14 of IgG1 subclass and its corresponding F(ab ¢ ) 2 fragment directed against LAM from M. tuberculosis strain H37Rv. MoAb SMITB14 was shown by immunofluorescence to bind to whole cells of the clinical isolate M. tuberculosis strain Harlingen as well as to M. tuberculosis H37Rv. The binding of MoAb SMITB14 to LAM was inhibited by arabinomannan (AM) and oligosaccharides (5·2 kDa) derived from LAM, showing that the MoAb binds specifically to the AM carbohydrate portion of LAM. In passive protection experiments BALB/c mice were infected intravenously with M. tuberculosis Harlingen. MoAb SMITB14 was added intravenously either prior to, or together with, the bacteria. The antibody proved to be protective against the M. tuberculosis infection in terms of a dose-dependent reduction in bacterial load in spleens and lungs, reduced weight loss and, most importantly, increased long-term survival.

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

“…To date, studies regarding the role of humoral immunity in the containment of M. tuberculosis or the development of tissue damage vary from study to study [14][15][16]. These discrepancies are probably due to the fact that different models and parameters of mAbs were used in these different studies for assessing the outcome of infection [17].…”

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.…”