{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,1,7]],"date-time":"2026-01-07T23:23:30Z","timestamp":1767828210217,"version":"3.49.0"},"reference-count":78,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2024,1,9]],"date-time":"2024-01-09T00:00:00Z","timestamp":1704758400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Immunol."],"abstract":"<jats:p>Human <jats:italic>Salmonella<\/jats:italic> infections pose significant public health challenges globally, primarily due to low diagnostic yield of systemic infections, emerging and expanding antibiotic resistance of both the typhoidal and non-typhoidal <jats:italic>Salmonella<\/jats:italic> strains and the development of asymptomatic carrier state that functions as a reservoir of infection in the community. The limited long-term efficacy of the currently licensed typhoid vaccines, especially in smaller children and non-availability of vaccines against other <jats:italic>Salmonella<\/jats:italic> serovars necessitate active research towards developing a multivalent vaccine with wider coverage of protection against pathogenic <jats:italic>Salmonella<\/jats:italic> serovars. We had earlier reported immunogenicity and protective efficacy of a subunit vaccine containing a recombinant outer membrane protein (T2544) of <jats:italic>Salmonella<\/jats:italic> Typhi in a mouse model. This was achieved through the robust induction of serum IgG, mucosal secretory IgA and <jats:italic>Salmonella<\/jats:italic>-specific cytotoxic T cells as well as memory B and T cell response. Here, we report the development of a glycoconjugate vaccine, containing high molecular weight complexes of <jats:italic>Salmonella<\/jats:italic> Typhimurium O-specific polysaccharide (OSP) and recombinant T2544 that conferred simultaneous protection against <jats:italic>S.<\/jats:italic> Typhi, <jats:italic>S.<\/jats:italic> Paratyphi, <jats:italic>S.<\/jats:italic> Typhimurium and cross-protection against <jats:italic>S.<\/jats:italic> enteritidis in mice. Our findings corroborate with the published studies that suggested the potential of <jats:italic>Salmonella<\/jats:italic> OSP as a vaccine antigen. The role of serum antibodies in vaccine-mediated protection is suggested by rapid seroconversion with high titers of serum IgG and IgA, persistently elevated titers after primary immunization along with a strong antibody recall response with higher avidity serum IgG against both OSP and T2544 and significantly raised SBA titers of both primary and secondary antibodies against different <jats:italic>Salmonella<\/jats:italic> serovars. Elevated intestinal secretory IgA and bacterial motility inhibition by the secretory antibodies supported their role as well in vaccine-induced protection. Finally, robust induction of T effector memory response indicates long term efficacy of the candidate vaccine. The above findings coupled with protection of vaccinated animals against multiple clinical isolates confirm the suitability of OSP-rT2544 as a broad-spectrum candidate subunit vaccine against human infection due to typhoidal and non-typhoidal <jats:italic>Salmonella<\/jats:italic> serovars.<\/jats:p>","DOI":"10.3389\/fimmu.2023.1304170","type":"journal-article","created":{"date-parts":[[2024,1,9]],"date-time":"2024-01-09T13:04:23Z","timestamp":1704805463000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":8,"title":["A candidate glycoconjugate vaccine induces protective antibodies in the serum and intestinal secretions, antibody recall response and memory T cells and protects against both typhoidal and non-typhoidal Salmonella serovars"],"prefix":"10.3389","volume":"14","author":[{"given":"Risha","family":"Haldar","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Amlanjyoti","family":"Dhar","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Debayan","family":"Ganguli","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Suparna","family":"Chakraborty","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Ananda","family":"Pal","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"George","family":"Banik","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Shin-ichi","family":"Miyoshi","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Santasabuj","family":"Das","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1965","published-online":{"date-parts":[[2024,1,9]]},"reference":[{"key":"B1","doi-asserted-by":"publisher","DOI":"10.1016\/S1473-3099(12)70028-2","article-title":"Community-acquired bacterial bloodstream infections in developing countries in south and southeast Asia: a systematic review","volume":"12","author":"Deen","year":"2012","journal-title":"Lancet Infect Dis"},{"key":"B2","doi-asserted-by":"publisher","first-page":"692","DOI":"10.1016\/S1473-3099(21)00615-0","article-title":"Complications and mortality of non-typhoidal salmonella invasive disease: a global systematic review and meta-analysis","volume":"22","author":"Marchello","year":"2022","journal-title":"Lancet Infect Dis"},{"key":"B3","doi-asserted-by":"publisher","DOI":"10.1093\/ofid\/ofad041","article-title":"Salmonella combination vaccines: moving beyond typhoid","volume":"10","author":"MacLennan","year":"2023","journal-title":"Open Forum Infect Dis"},{"key":"B4","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMoa2035916","article-title":"Safety and efficacy of a typhoid conjugate vaccine in Malawian children","volume":"385","author":"Patel","year":"2021","journal-title":"N Engl J Med"},{"key":"B5","doi-asserted-by":"publisher","DOI":"10.1016\/S0140-6736(21)01124-7","article-title":"Protection by vaccination of children against typhoid fever with a Vi-tetanus toxoid conjugate vaccine in urban Bangladesh: a cluster-randomised trial","volume":"398","author":"Qadri","year":"2021","journal-title":"Lancet"},{"key":"B6","doi-asserted-by":"publisher","DOI":"10.1016\/S2214-109X(21)00346-6","article-title":"Efficacy of typhoid conjugate vaccine in Nepal: final results of a phase 3, randomised, controlled trial","volume":"9","author":"Shakya","year":"2021","journal-title":"Lancet Glob Health"},{"key":"B7","doi-asserted-by":"publisher","DOI":"10.1016\/0264-410x(90)90183-m","article-title":"Efficacy of one or two doses of Ty21a Salmonella typhi vaccine in enteric-coated capsules in a controlled field trial","volume":"8","author":"Black","year":"1990","journal-title":"Chilean Typhoid Commit Vaccine"},{"key":"B8","doi-asserted-by":"publisher","DOI":"10.4161\/hv.29054","article-title":"Vaccines against invasive Salmonella disease: current status and future directions","volume":"10","author":"MacLennan","year":"2014","journal-title":"Hum Vaccin Immunother"},{"key":"B9","doi-asserted-by":"publisher","DOI":"10.4014\/jmb.0812.675","article-title":"Overexpression, purification, and immunogenicity of recombinant porin proteins of Salmonella enterica serovar Typhi (S. 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