{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,1]],"date-time":"2026-08-01T10:03:21Z","timestamp":1785578601028,"version":"3.56.0"},"reference-count":84,"publisher":"Oxford University Press (OUP)","issue":"6","license":[{"start":{"date-parts":[[2025,4,26]],"date-time":"2025-04-26T00:00:00Z","timestamp":1745625600000},"content-version":"vor","delay-in-days":2,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/100000060","name":"National Institute of Allergy and Infectious Diseases","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100000060","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000002","name":"National Institutes of Health","doi-asserted-by":"publisher","award":["R01AI125160"],"award-info":[{"award-number":["R01AI125160"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000002","name":"National Institutes of Health","doi-asserted-by":"publisher","award":["R01AI181218"],"award-info":[{"award-number":["R01AI181218"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2025,4,26]]},"abstract":"<jats:title>Abstract<\/jats:title>\n               <jats:p>Tuberculosis (TB) is again the deadliest infectious disease globally, and more efficacious vaccines are needed to reduce this mortality. Successful subunit TB vaccines need antigens and adjuvants that are immunogenic, inexpensive, and accessible. Here we evaluated the potential of synthetically produced Monophosphoryl lipid A (SyMLP), a TLR4-agonist, formulated in an oil-in-water emulsion (EmT4\u2122) in combination with selected fusion proteins, to drive an effective vaccine-mediated immunogenic response in C57BL\/6 mice against Mycobacterium tuberculosis (M.tb) HN878 and H37Rv challenge. We first observed that EmT4\u2122 enhances activation of C57BL\/6 bone-marrow derived macrophages and dendritic cells measured by CD40, CD86, and MHCII expression by flow cytometry. EmT4\u2122 did not induce safety signals in a scaled tolerability study. In immunogenicity studies, mice immunized 3 times 3 weeks apart with ID93 antigen + EmT4\u2122 produced a significantly higher magnitude of circulating proinflammatory cytokines and ID93-specific immunoglobulin G (IgG) antibodies pre- and post-challenge with M.tb than saline control animals. Ex vivo ID93 restimulated splenocytes and lung cells elicited significant polyfunctional CD4+ T-helper 1 responses. Importantly, ID93\u2009+\u2009EmT4\u2122 immunizations significantly reduced bacterial burden in C57BL\/6 mice 4\u2009weeks post-challenge. Interestingly, EmT4\u2122 paired with a next generation protein fusion ID91 also afforded prophylactic protection against M.tb HN878 challenge in both young (6 to 8\u2009wk) and aged (20\u2009mo) immunocompromised Beige mice. These protection and immunogenicity findings suggest that synthetically derived EmT4\u2122 adjuvant is not only suitable to help backfill the preclinical TB vaccine candidate pipeline but is also suitable for the needs of the global community.<\/jats:p>","DOI":"10.1093\/immhor\/vlaf014","type":"journal-article","created":{"date-parts":[[2025,4,26]],"date-time":"2025-04-26T07:16:52Z","timestamp":1745651812000},"source":"Crossref","is-referenced-by-count":2,"title":["Characterizing TLR4 agonist EmT4\u2122 as an anti-<i>Mycobacterium tuberculosis<\/i> vaccine adjuvant"],"prefix":"10.1093","volume":"9","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-5034-9727","authenticated-orcid":false,"given":"Sasha E","family":"Larsen","sequence":"first","affiliation":[{"name":"Center for Global Infectious Disease Research, Seattle Children's Research Institute, Seattle Children's Hospital , Seattle, WA,","place":["United States"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Maham","family":"Rais","sequence":"additional","affiliation":[{"name":"Center for Global Infectious Disease Research, Seattle Children's Research Institute, Seattle Children's Hospital , Seattle, WA,","place":["United States"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Valerie A","family":"Reese","sequence":"additional","affiliation":[{"name":"Center for Global Infectious Disease Research, Seattle Children's Research Institute, Seattle Children's Hospital , Seattle, WA,","place":["United States"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Debora","family":"Ferede","sequence":"additional","affiliation":[{"name":"Center for Global Infectious Disease Research, Seattle Children's Research Institute, Seattle Children's Hospital , Seattle, WA,","place":["United 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