{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,5,27]],"date-time":"2026-05-27T18:06:17Z","timestamp":1779905177746,"version":"3.53.1"},"reference-count":43,"publisher":"Public Library of Science (PLoS)","issue":"5","license":[{"start":{"date-parts":[[2026,5,27]],"date-time":"2026-05-27T00:00:00Z","timestamp":1779840000000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100000780","name":"European Commission","doi-asserted-by":"publisher","award":["101080462"],"award-info":[{"award-number":["101080462"]}],"id":[{"id":"10.13039\/501100000780","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000865","name":"Bill and Melinda Gates Foundation","doi-asserted-by":"publisher","award":["INV-058519"],"award-info":[{"award-number":["INV-058519"]}],"id":[{"id":"10.13039\/100000865","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100003977","name":"Israel Science Foundation","doi-asserted-by":"publisher","award":["3136\/22"],"award-info":[{"award-number":["3136\/22"]}],"id":[{"id":"10.13039\/501100003977","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100003977","name":"Israel Science Foundation","doi-asserted-by":"publisher","award":["638\/23"],"award-info":[{"award-number":["638\/23"]}],"id":[{"id":"10.13039\/501100003977","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100006221","name":"United States - Israel Binational Science Foundation","doi-asserted-by":"publisher","award":["01031771"],"award-info":[{"award-number":["01031771"]}],"id":[{"id":"10.13039\/100006221","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["www.plospathogens.org"],"crossmark-restriction":false},"short-container-title":["PLoS Pathog"],"abstract":"<jats:p>\n                    The role of antibodies in the host response against\n                    <jats:italic>Mycobacterium tuberculosis<\/jats:italic>\n                    (\n                    <jats:italic>M. tb<\/jats:italic>\n                    ) bacteria is still poorly understood. We previously isolated two monoclonal antibodies (mAbs), p4-36 and p4-163, from an\n                    <jats:italic>M. tb<\/jats:italic>\n                    infected donor that target two non-overlapping epitopes on PstS1, a subunit of the\n                    <jats:italic>M. tb<\/jats:italic>\n                    phosphate transporter. Although these antibodies reduced lung bacterial burden in mice (30\u201340% reduction in CFU), their efficacy remained modest for therapeutic application. Here, we employed a rational antibody engineering approach to further enhance their anti-\n                    <jats:italic>M. tb<\/jats:italic>\n                    potency. Affinity maturation of p4-163 yielded p4-163LR, a variant with superior binding to PstS1 and improved recognition of live, attenuated\n                    <jats:italic>M. tb<\/jats:italic>\n                    . Surprisingly, p4-163LR alone did not confer enhanced protection against virulent\n                    <jats:italic>M. tb in vivo<\/jats:italic>\n                    . However, the generation of a bispecific antibody combining p4-36 and p4-163LR (Bi-S 36\/163LR) significantly improved bacterial binding and antibody-dependent cellular phagocytosis (ADCP). Notably, prophylactic administration of Bi-S 36\/163LR led to a\u2009~\u20091 log reduction in lung bacterial burden compared to control animals treated with isotype control. These findings define a novel, structure-guided strategy to amplify the functional capacity of natural anti-\n                    <jats:italic>M. tb<\/jats:italic>\n                    antibodies and highlight bispecific antibody platforms as promising candidates for host-directed tuberculosis immunotherapy.\n                  <\/jats:p>","DOI":"10.1371\/journal.ppat.1014133","type":"journal-article","created":{"date-parts":[[2026,5,27]],"date-time":"2026-05-27T17:38:20Z","timestamp":1779903500000},"page":"e1014133","update-policy":"https:\/\/doi.org\/10.1371\/journal.ppat.corrections_policy","source":"Crossref","is-referenced-by-count":0,"title":["Modified Anti-PstS1 Bi-specific antibodies unlock potent protection against tuberculosis"],"prefix":"10.1371","volume":"22","author":[{"family":"Akanksha","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rania","family":"Bouzeyen","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Avia","family":"Watson","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Gil","family":"Wiseglass","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nyaradzai","family":"Sithole","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lilach","family":"Abramovitz","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Noam","family":"Ben-Shalom","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rotem","family":"Rubinstein","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Babak","family":"Javid","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5386-502X","authenticated-orcid":true,"given":"Natalia T.","family":"Freund","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"340","published-online":{"date-parts":[[2026,5,27]]},"reference":[{"key":"ppat.1014133.ref001","unstructured":"World Health O. 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Burden in human macrophages and in mice by enhancing autophagy and phagosome maturation","volume":"209","author":"SP Parihar","year":"2014","journal-title":"Journal of Infectious Diseases"},{"key":"ppat.1014133.ref043","doi-asserted-by":"crossref","DOI":"10.3389\/fimmu.2024.1463224","article-title":"Metformin improves Infection by strengthening macrophage antimicrobial functions","volume":"15","author":"SD Mediaas","year":"2024","journal-title":"Frontiers in Immunology"}],"container-title":["PLOS Pathogens"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/dx.plos.org\/10.1371\/journal.ppat.1014133","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,5,27]],"date-time":"2026-05-27T17:38:27Z","timestamp":1779903507000},"score":1,"resource":{"primary":{"URL":"https:\/\/dx.plos.org\/10.1371\/journal.ppat.1014133"}},"subtitle":[],"editor":[{"given":"Padmini","family":"Salgame","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"editor"}]}],"short-title":[],"issued":{"date-parts":[[2026,5,27]]},"references-count":43,"journal-issue":{"issue":"5","published-online":{"date-parts":[[2026,5,27]]}},"URL":"https:\/\/doi.org\/10.1371\/journal.ppat.1014133","relation":{},"ISSN":["1553-7374"],"issn-type":[{"value":"1553-7374","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,5,27]]}}}