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An immunocompromised host status, either genetically or acutely acquired, presents a large risk for progressive NTM infections. Due to this quietly emerging health threat, we evaluated the ability of a recombinant fusion protein ID91 combined with GLA-SE [<jats:underline>g<\/jats:underline>lucopyranosyl<jats:underline>l<\/jats:underline>ipid<jats:underline>a<\/jats:underline>djuvant, a toll like receptor 4 agonist formulated in an oil-in-water<jats:underline>s<\/jats:underline>table nano-<jats:underline>e<\/jats:underline>mulsion] to confer protection in both C57BL\/6 (wild type) and Beige (immunocompromised) mouse models. We optimized an aerosol challenge model using a clinical NTM isolate:<jats:italic>M. avium<\/jats:italic>2-151 smt, observed bacterial growth kinetics, colony morphology, drug sensitivity and histopathology, characterized the influx of pulmonary immune cells, and confirmed the immunogenicity of ID91 in both mouse models. To determine prophylactic vaccine efficacy against this<jats:italic>M. avium<\/jats:italic>isolate, mice were immunized with either ID91\u2009+\u2009GLA-SE or bacillus Calmette\u2013Gu\u00e9rin (BCG)<jats:italic>.<\/jats:italic>Immunocompromised Beige mice displayed a delayed influx of innate and adaptive immune cells resulting in a sustained and increased bacterial burden in the lungs and spleen compared to C57BL\/6 mice. Importantly, both ID91\u2009+\u2009GLA-SE and BCG vaccines significantly reduced pulmonary bacterial burden in both mouse strains. This work is a proof-of-concept study of subunit vaccine-induced protection against NTM.<\/jats:p>","DOI":"10.1038\/s41598-021-88291-8","type":"journal-article","created":{"date-parts":[[2021,4,27]],"date-time":"2021-04-27T10:13:30Z","timestamp":1619518410000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":26,"title":["Subunit vaccine protects against a clinical isolate of Mycobacterium avium in wild type and immunocompromised mouse models"],"prefix":"10.1038","volume":"11","author":[{"given":"Sasha E.","family":"Larsen","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Valerie A.","family":"Reese","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tiffany","family":"Pecor","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Bryan J.","family":"Berube","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sarah K.","family":"Cooper","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Guy","family":"Brewer","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Diane","family":"Ordway","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Marcela","family":"Henao-Tamayo","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Brendan K.","family":"Podell","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Susan L.","family":"Baldwin","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rhea N.","family":"Coler","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2021,4,27]]},"reference":[{"key":"88291_CR1","doi-asserted-by":"publisher","first-page":"1458","DOI":"10.1513\/AnnalsATS.201503-173OC","volume":"12","author":"SE Strollo","year":"2015","unstructured":"Strollo, S. 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