{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,3]],"date-time":"2026-10-03T14:26:55Z","timestamp":1791037615600,"version":"4.1.0"},"reference-count":106,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2026,3,20]],"date-time":"2026-03-20T00:00:00Z","timestamp":1773964800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100001411","name":"Indian Council of Medical Research","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100001411","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001407","name":"Department of Biotechnology, Ministry of Science and Technology, India","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100001407","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Immunol."],"abstract":"<jats:sec>\n                    <jats:title>Introduction<\/jats:title>\n                    <jats:p>\n                      <jats:italic>Leptospira<\/jats:italic>\n                      , a zoonotic pathogen, poses a significant public health threat, causing morbidity and mortality in both humans and animals. Although several bacterin and recombinant vaccines targeting specific serovars have been developed, most provide short-term, serovar-restricted protection and do not consistently induce sterilizing immunity or broad cross-serovar coverage.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Materials<\/jats:title>\n                    <jats:p>To address this challenge, we employed comparative pan-genomic analysis and reverse vaccinology to identify conserved potential vaccine candidates (PVCs) and designed a multi-epitope vaccine (MEV) incorporating highly immunogenic B- and T-cell epitopes. Unlike previous studies largely limited to computational prediction or a small number of known antigens, our strategy integrates soft-core genome-wide antigen prioritization with structural validation and experimental evaluation of innate and adaptive immune responses. Selected epitopes were linked with appropriate spacers and fused to a TLR4 agonist (APPHALS) at the N-terminus to enhance immune activation.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results and discussion<\/jats:title>\n                    <jats:p>\n                      <jats:italic>In silico<\/jats:italic>\n                      analyses confirmed the stability and immunogenic potential of the MEV construct. The purified recombinant MEV reacted strongly with hyperimmune and clinical sera. Anti-MEV antibodies agglutinated multiple pathogenic\n                      <jats:italic>Leptospira<\/jats:italic>\n                      serovars and inhibited bacterial growth\n                      <jats:italic>in vitro<\/jats:italic>\n                      . MEV stimulation induced macrophage activation, evidenced by increased proinflammatory cytokine production and upregulation of co-stimulatory molecules. Immunization in mice elicited robust humoral and T-cell responses. Collectively, these findings position MEV as a rationally designed next-generation vaccine candidate with potential for broad cross-protective immunity against leptospirosis.\n                    <\/jats:p>\n                  <\/jats:sec>","DOI":"10.3389\/fimmu.2026.1774717","type":"journal-article","created":{"date-parts":[[2026,3,20]],"date-time":"2026-03-20T06:36:42Z","timestamp":1773988602000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":3,"title":["A multi-epitope approach for development of a universal vaccine against leptospirosis"],"prefix":"10.3389","volume":"17","author":[{"given":"Mohd","family":"Abdullah","sequence":"first","affiliation":[{"name":"Laboratory of Vaccine Immunology, National Institute of Animal Biotechnology","place":["Hyderabad, India"]},{"name":"Laboratory of Genomics and Computational Biology, National Institute of Animal Biotechnology","place":["Hyderabad, India"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mohammad","family":"Kadivella","sequence":"additional","affiliation":[{"name":"Laboratory of Vaccine Immunology, National Institute of Animal Biotechnology","place":["Hyderabad, India"]},{"name":"Regional Centre for Biotechnology","place":["Faridabad, India"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Pallavi","family":"Vyas","sequence":"additional","affiliation":[{"name":"Laboratory of Vaccine Immunology, National Institute of Animal Biotechnology","place":["Hyderabad, India"]},{"name":"Regional Centre for Biotechnology","place":["Faridabad, India"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jusail","family":"C. P.","sequence":"additional","affiliation":[{"name":"Laboratory of Vaccine Immunology, National Institute of Animal Biotechnology","place":["Hyderabad, India"]},{"name":"Regional Centre for Biotechnology","place":["Faridabad, India"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Bothammal","family":"Palanisamy","sequence":"additional","affiliation":[{"name":"Laboratory of Vaccine Immunology, National Institute of Animal Biotechnology","place":["Hyderabad, India"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sarwar","family":"Azam","sequence":"additional","affiliation":[{"name":"Laboratory of Genomics and Computational Biology, National Institute of Animal Biotechnology","place":["Hyderabad, India"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Syed M.","family":"Faisal","sequence":"additional","affiliation":[{"name":"Laboratory of Vaccine Immunology, National Institute of Animal Biotechnology","place":["Hyderabad, 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