Isolation and characterization of a protective monoclonal antibody targeting outer membrane protein (OmpA) against tuberculosis

In this study, we identified a protective antibody targeting the outer membrane protein (OmpA) of <i>Mycobacterium tuberculosis</i>. This monoclonal antibody (MAb) belongs to the IgG2b isotype and exhibits high titers of 1:2,048,000 to the antigen. The cell infection assays demonstrated that antibody protection was achieved by promoting opsonophagocytosis in a dose-dependent manner, enhancing phagosome-lysosome fusion, and inhibiting mycobacterial intracellular growth <i>in vitro</i> and <i>ex vivo</i>. Cytotoxicity assays, animal toxicity analyses, and pharmacokinetic evaluations confirmed the safety and sustained effectiveness of the antibody <i>in vivo</i>. Furthermore, the mAb 1E1 can reduce the organs' bacterial burdens and pathological damages in the prevention mouse model as well as the treatment models. Above all, in this study, we found a novel mAb named 1E1 with IgG2b isotype targeting OmpA can have protection against tuberculosis (TB) in mice, which may serve as a treatment strategy for drug-resistant TB and a promising antigen for TB vaccine development.