Citation:
Avia Watson, Li, Hao , Ma, Bingting , Weiss, Ronen , Bendayan, Daniele , Abramovitz, Lilach , Ben-Shalom, Noam , Mor, Michael , Pinko, Erica , Bar Oz, Michal , Wang, Zhenqi , Du, Fengjiao , Lu, Yu , Rybniker, Jan , Dahan, Rony , Huang, Hairong , Barkan, Daniel , Xiang, Ye , Javid, Babak , and Freund, Natalia T. 2021.
“Human Antibodies Targeting A Mycobacterium Transporter Protein Mediate Protection Against Tuberculosis”. Nature Communications, 12. doi:10.1038/s41467-021-20930-0.
Abstract:
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.Notes:
Publisher Copyright: © 2021, The Author(s).
