{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,23]],"date-time":"2026-09-23T23:44:40Z","timestamp":1790207080732,"version":"4.1.0"},"reference-count":57,"publisher":"MDPI AG","issue":"12","license":[{"start":{"date-parts":[[2023,12,6]],"date-time":"2023-12-06T00:00:00Z","timestamp":1701820800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100001409","name":"Department of Science and Technology under the Ministry of Science and Technology, Government of India","doi-asserted-by":"publisher","award":["EMR\/2017\/002468 (SP046)"],"award-info":[{"award-number":["EMR\/2017\/002468 (SP046)"]}],"id":[{"id":"10.13039\/501100001409","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001409","name":"Department of Science and Technology under the Ministry of Science and Technology, Government of India","doi-asserted-by":"publisher","award":["C0023"],"award-info":[{"award-number":["C0023"]}],"id":[{"id":"10.13039\/501100001409","id-type":"DOI","asserted-by":"publisher"}]},{"name":"NIAB","award":["EMR\/2017\/002468 (SP046)"],"award-info":[{"award-number":["EMR\/2017\/002468 (SP046)"]}]},{"name":"NIAB","award":["C0023"],"award-info":[{"award-number":["C0023"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Vaccines"],"abstract":"<jats:p>Leptospirosis is a globally significant zoonotic disease. The current inactivated vaccine offers protection against specific serovars but does not provide complete immunity. Various surface antigens, such as Leptospira immunoglobulin-like proteins (LigA and LigB), have been identified as potential subunit vaccine candidates. However, these antigens require potent adjuvants for effectiveness. Bacterial lipopolysaccharides (LPSs), including lipid A, are a well-known immunostimulant, and clinical adjuvants often contain monophosphoryl lipid A (MPLA). Being less endotoxic, we investigated the adjuvant properties of lipid A isolated from L. interrogans serovar Pomona (PLA) in activating innate immunity and enhancing antigen-specific adaptive immune responses. PLA activated macrophages to a similar degree as MPLA, albeit at a higher dose, suggesting that it is less potent in stimulation than MPLA. Mice immunized with a variable portion of LigA (LAV) combined with alum and PLA (LAV-alum-PLA) exhibited significantly higher levels of LAV-specific humoral and cellular immune responses compared to alum alone but similar to those induced by alum-MPLA. The adjuvant activity of PLA resembles that of MPLA and is primarily achieved through the increased recruitment, activation, and uptake of antigens by innate immune cells. Furthermore, like MPLA, PLA formulation establishes a long-lasting memory response. Notably, PLA demonstrated superior potency than MPLA formulation and provided sterilizing immunity against the leptospirosis in a hamster model. Overall, our study sheds light on the adjuvant properties of Leptospira lipid A and offers promising avenues for developing LPS-based vaccines against this devastating zoonotic disease.<\/jats:p>","DOI":"10.3390\/vaccines11121824","type":"journal-article","created":{"date-parts":[[2023,12,6]],"date-time":"2023-12-06T08:48:32Z","timestamp":1701852512000},"page":"1824","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":3,"title":["Leptospira Lipid A Is a Potent Adjuvant That Induces Sterilizing Immunity against Leptospirosis"],"prefix":"10.3390","volume":"11","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-4587-5719","authenticated-orcid":false,"given":"Vivek P.","family":"Varma","sequence":"first","affiliation":[{"name":"Laboratory of Vaccine Immunology, National Institute of Animal Biotechnology, Hyderabad 500032, India"},{"name":"Graduate Studies, Manipal Academy of Higher Education, Manipal 576104, India"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3565-1543","authenticated-orcid":false,"given":"Mohammad","family":"Kadivella","sequence":"additional","affiliation":[{"name":"Laboratory of Vaccine Immunology, National Institute of Animal Biotechnology, Hyderabad 500032, India"},{"name":"Regional Centre for Biotechnology, Faridabad 121001, India"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3676-4822","authenticated-orcid":false,"given":"Sridhar","family":"Kavela","sequence":"additional","affiliation":[{"name":"Laboratory of Vaccine Immunology, National Institute of Animal Biotechnology, Hyderabad 500032, India"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8736-5170","authenticated-orcid":false,"given":"Syed M.","family":"Faisal","sequence":"additional","affiliation":[{"name":"Laboratory of Vaccine Immunology, National Institute of Animal Biotechnology, Hyderabad 500032, India"},{"name":"Regional Centre for Biotechnology, Faridabad 121001, India"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2023,12,6]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","unstructured":"Costa, F., Hagan, J.E., Calcagno, J., Kane, M., Torgerson, P., Martinez-Silveira, M.S., Stein, C., Abela-Ridder, B., and Ko, A.I. 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