TY - JOUR TI - Human antibodies targeting a Mycobacterium transporter protein mediate protection against tuberculosis AU - Watson, Avia AU - Li, Hao AU - Ma, Bingting AU - Weiss, Ronen AU - Bendayan, Daniele AU - Abramovitz, Lilach AU - Ben-Shalom, Noam AU - Mor, Michael AU - Pinko, Erica AU - Bar Oz, Michal AU - Wang, Zhenqi AU - Du, Fengjiao AU - Lu, Yu AU - Rybniker, Jan AU - Dahan, Rony AU - Huang, Hairong AU - Barkan, Daniel AU - Xiang, Ye AU - Javid, Babak AU - Freund, Natalia T. T2 - Nature Communications AB - Mycobacterium tuberculosis (Mtb) exposure drives antibody responses, but whether patients with active tuberculosis elicit protective antibodies, and against which antigens, is still unclear. Here we generate monoclonal antibodies from memory B cells of one patient to investigate the B cell responses during active infection. The antibodies, members of four distinct B cell clones, are directed against the Mtb phosphate transporter subunit PstS1. Antibodies p4-36 and p4-163 reduce Mycobacterium bovis-BCG and Mtb levels in an ex vivo human whole blood growth inhibition assay in an FcR-dependent manner; meanwhile, germline versions of p4-36 and p4-163 do not bind Mtb. Crystal structures of p4-36 and p4-170, complexed to PstS1, are determined at 2.1 Å and 2.4 Å resolution, respectively, to reveal two distinctive PstS1 epitopes. Lastly, a prophylactic p4-36 and p4-163 treatment in Mtb-infected Balb/c mice reduces bacterial lung burden by 50%. Our study shows that inhibitory anti-PstS1 B cell responses arise during active tuberculosis. DA - 2021/01/27/ PY - 2021 DO - 10.1038/s41467-021-20930-0 DP - www.nature.com VL - 12 IS - 1 SP - 602 LA - en SN - 2041-1723 UR - https://www.nature.com/articles/s41467-021-20930-0 Y2 - 2021/01/29/22:33:54 ER -