Human antibodies targeting a Mycobacterium transporter protein mediate protection against tuberculosis

Avia Watson, Hao Li, Bingting Ma, Ronen Weiss, Daniele Bendayan, Lilach Abramovitz, Noam Ben-Shalom, Michael Mor, Erica Pinko, Michal Bar Oz, Zhenqi Wang, Fengjiao Du, Yu Lu, Jan Rybniker, Rony Dahan, Hairong Huang, Daniel Barkan, Ye Xiang (), Babak Javid () and Natalia T. Freund ()
Additional contact information
Avia Watson: Tel Aviv University
Hao Li: Tsinghua University School of Medicine
Bingting Ma: Tsinghua University School of Medicine
Ronen Weiss: Tel Aviv University
Daniele Bendayan: Shmuel Harofe Hospital
Lilach Abramovitz: Tel Aviv University
Noam Ben-Shalom: Tel Aviv University
Michael Mor: Tel Aviv University
Erica Pinko: Shmuel Harofe Hospital
Michal Bar Oz: The Hebrew University of Jerusalem
Zhenqi Wang: Tsinghua University School of Medicine
Fengjiao Du: Beijing Chest Hospital, Capital Medical University
Yu Lu: Beijing Chest Hospital, Capital Medical University
Jan Rybniker: Department of Internal Medicine, Division of Infectious Diseases, University of Cologne
Rony Dahan: Weizmann Institute of Science
Hairong Huang: Capital Medical University, Beijing Tuberculosis and Thoracic Tumor Institute
Daniel Barkan: The Hebrew University of Jerusalem
Ye Xiang: Tsinghua University School of Medicine
Babak Javid: Tsinghua University School of Medicine
Natalia T. Freund: Tel Aviv University

Nature Communications, 2021, vol. 12, issue 1, 1-11

Abstract: 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.

Date: 2021
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DOI: 10.1038/s41467-021-20930-0

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