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Intravenous (i.v.) vaccination with Bacille Calmette\u2013Gu\u00e9rin (BCG) provides nearly complete protection against TB in rhesus macaques, but the antibody response it elicits remains incompletely defined. Here we show that i.v. BCG drives superior antibody responses in the plasma and the lungs of rhesus macaques compared to traditional intradermal BCG administration. While i.v. BCG broadly expands antibody titers and functions, IgM titers in the plasma and lungs of immunized macaques are among the strongest markers of reduced bacterial burden. IgM was also enriched in macaques that received protective vaccination with an attenuated strain of\n                    <jats:italic>Mtb<\/jats:italic>\n                    . Finally, an\n                    <jats:italic>Mtb<\/jats:italic>\n                    -specific IgM monoclonal antibody reduced\n                    <jats:italic>Mtb<\/jats:italic>\n                    survival in vitro. Collectively, these data highlight the potential importance of IgM responses as a marker and mediator of protection against TB.\n                  <\/jats:p>","DOI":"10.1038\/s41590-021-01066-1","type":"journal-article","created":{"date-parts":[[2021,11,22]],"date-time":"2021-11-22T12:03:42Z","timestamp":1637582622000},"page":"1515-1523","update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":125,"title":["Robust IgM responses following intravenous vaccination with Bacille Calmette\u2013Gu\u00e9rin associate with prevention of Mycobacterium tuberculosis infection in macaques"],"prefix":"10.1038","volume":"22","author":[{"given":"Edward B.","family":"Irvine","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Anthony","family":"O\u2019Neil","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0035-2802","authenticated-orcid":false,"given":"Patricia A.","family":"Darrah","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sally","family":"Shin","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2933-9812","authenticated-orcid":false,"given":"Alok","family":"Choudhary","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5335-7386","authenticated-orcid":false,"given":"Wenjun","family":"Li","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"William","family":"Honnen","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Smriti","family":"Mehra","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3521-1257","authenticated-orcid":false,"given":"Deepak","family":"Kaushal","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4443-2134","authenticated-orcid":false,"given":"Hannah Priyadarshini","family":"Gideon","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7874-8981","authenticated-orcid":false,"given":"JoAnne L.","family":"Flynn","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mario","family":"Roederer","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3133-0849","authenticated-orcid":false,"given":"Robert A.","family":"Seder","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Abraham","family":"Pinter","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7565-9975","authenticated-orcid":false,"given":"Sarah","family":"Fortune","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7680-9215","authenticated-orcid":false,"given":"Galit","family":"Alter","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2021,11,22]]},"reference":[{"key":"1066_CR1","unstructured":"World Health Organization. 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