最新發表論文
Features and protective efficacy of human monoclonal antibodies targeting Mycobacterium tuberculosis arabinomannan

A better understanding of the epitopes most relevant for antibody-mediated protection against tuberculosis (TB) remains a major knowledge gap. We have shown that human polyclonal IgG to the Mycobacterium tuberculosis (Mtb) surface glycan arabinomannan (AM) and related lipoarabinomannan (LAM) is protective against TB. To investigate the impact of AM epitope recognition and Fc-gamma receptor (FcgR)-binding on antibody functions against Mtb, we isolated a high-affinity human monoclonal antibody (mAb; P1AM25) to AM and show its binding to oligosaccharide (OS) motifs we previously found to be associated with in vitro functions of human polyclonal anti-AM IgG. Human IgG1 P1AM25, but not two other high-affinity human IgG1 anti-AM mAbs reactive with different AM OS motifs, enhanced Mtb phagocytosis by macrophages and reduced intracellular growth in an FcgR-dependent manner. P1AM25 in murine IgG2a, but neither murine IgG1 nor a non-FcgR-binding IgG, given intraperitoneally prior to and after aerosolized Mtb infection was protective in C57BL/6 mice. Moreover, we demonstrate the protective efficacy of human IgG1 P1AM25 in passive transfer with Mtb-infected FcgR-humanized mice. These data enhance our knowledge of the important interplay between both antibody epitope specificity and Fc effector functions in the defense against Mtb and could inform development strategies of vaccines against TB.