TY - JOUR
T1 - 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.
N1 - Publisher Copyright:
© 2021, The Author(s).
PY - 2021/12/1
Y1 - 2021/12/1
N2 - 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.
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.
UR - http://www.scopus.com/inward/record.url?scp=85099942696&partnerID=8YFLogxK
U2 - 10.1038/s41467-021-20930-0
DO - 10.1038/s41467-021-20930-0
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C2 - 33504803
AN - SCOPUS:85099942696
SN - 2041-1723
VL - 12
JO - Nature Communications
JF - Nature Communications
IS - 1
M1 - 602
ER -