{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,27]],"date-time":"2026-07-27T06:01:52Z","timestamp":1785132112093,"version":"3.55.0"},"reference-count":54,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2026,7,27]],"date-time":"2026-07-27T00:00:00Z","timestamp":1785110400000},"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:sec>\n                    <jats:title>Introduction<\/jats:title>\n                    <jats:p>\n                      <jats:italic>Salmonella<\/jats:italic>\n                      and\n                      <jats:italic>Shigella<\/jats:italic>\n                      infections are two of the leading causes of global diarrheal deaths in children younger than 5 years. Licensed vaccines against\n                      <jats:italic>Salmonella<\/jats:italic>\n                      Typhi have been shown to be effective, and other\n                      <jats:italic>Salmonella<\/jats:italic>\n                      and\n                      <jats:italic>Shigella<\/jats:italic>\n                      vaccine candidates are being evaluated in clinical trials.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>\n                      We have previously described two 4-valent vaccines against\n                      <jats:italic>Salmonella<\/jats:italic>\n                      and\n                      <jats:italic>Shigella<\/jats:italic>\n                      strains separately. Here, we tested the combination of\n                      <jats:italic>Salmonella<\/jats:italic>\n                      and\n                      <jats:italic>Shigella<\/jats:italic>\n                      vaccines in animal models. ELISA was used to determine antibody titers against antigens, and bactericidal and opsonophagocytic assays were used to determine the function of these antibodies.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results and discussion<\/jats:title>\n                    <jats:p>\n                      We found that the 8-valent\n                      <jats:italic>Salmonella\/Shigella<\/jats:italic>\n                      vaccine induced immune responses similar to those of the two 4-valent counterparts. The immunological benefits of the addition of the adjuvant aluminum phosphate (alum), R848\/Alum, or AddaS03 were evaluated in rabbits. The results demonstrated that alum augments antibody production against vaccine protein components, and the addition of R848\/Alum or AddaS03 significantly enhanced antibody production and bactericidal activity for some serotypes.\n                    <\/jats:p>\n                  <\/jats:sec>","DOI":"10.3389\/fimmu.2026.1886839","type":"journal-article","created":{"date-parts":[[2026,7,27]],"date-time":"2026-07-27T05:41:11Z","timestamp":1785130871000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":0,"title":["Development of an 8-valent Salmonella and Shigella MAPS vaccine"],"prefix":"10.3389","volume":"17","author":[{"given":"Emily M.","family":"Boerth","sequence":"first","affiliation":[{"name":"Division of Infectious Diseases, Boston Children\u2019s Hospital, Harvard Medical School","place":["Boston, MA, United States"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Becky","family":"Roffler","sequence":"additional","affiliation":[{"name":"Division of Infectious Diseases, Boston Children\u2019s Hospital, Harvard Medical School","place":["Boston, MA, United States"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zoe","family":"Hancock","sequence":"additional","affiliation":[{"name":"Division of Infectious Diseases, Boston Children\u2019s Hospital, Harvard Medical School","place":["Boston, MA, United States"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Joyce","family":"Gong","sequence":"additional","affiliation":[{"name":"Division of Infectious Diseases, Boston Children\u2019s Hospital, Harvard Medical School","place":["Boston, MA, United States"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Calman A.","family":"MacLennan","sequence":"additional","affiliation":[{"name":"Calman MacLennan Consulting Ltd","place":["Abingdon-on-Thames, United Kingdom"]},{"name":"Department of Immunology and Immunotherapy, School of Medical and Dental Sciences, University of Birmingham","place":["Birmingham, United Kingdom"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Fan","family":"Zhang","sequence":"additional","affiliation":[{"name":"Division of Infectious Diseases, Boston Children\u2019s Hospital, Harvard Medical School","place":["Boston, MA, United States"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ying-Jie","family":"Lu","sequence":"additional","affiliation":[{"name":"Division of Infectious Diseases, Boston Children\u2019s Hospital, Harvard Medical School","place":["Boston, MA, United States"]}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1965","published-online":{"date-parts":[[2026,7,27]]},"reference":[{"key":"B1","doi-asserted-by":"publisher","DOI":"10.1016\/j.eclinm.2024.102883","article-title":"The global burden of enteric fever, 2017-2021: a systematic analysis from the global burden of disease study 2021","volume":"77","author":"Piovani","year":"2024","journal-title":"EClinicalMedicine"},{"key":"B2","doi-asserted-by":"publisher","DOI":"10.1016\/S1473-3099(24)00691-1","article-title":"Global, regional, and national age-sex-specific burden of diarrhoeal diseases, their risk factors, and aetiologies, 1990\u20132021, for 204 countries and territories: a systematic analysis for the Global Burden of Disease Study 2021","volume":"25","author":"Kyu","year":"2025","journal-title":"Lancet Infect Dis"},{"key":"B3","doi-asserted-by":"publisher","DOI":"10.1016\/j.tmaid.2022.102293","article-title":"Bacterial travellers' diarrhoea: a narrative review of literature published over the past 10 years","volume":"47","author":"Lomicronpez-Velez","year":"2022","journal-title":"Travel Med Infect Dis"},{"key":"B4","doi-asserted-by":"publisher","DOI":"10.1017\/S0950268823001693","article-title":"Prevalence and distribution of non-typhoidal Salmonella enterica serogroups and serovars isolated from normally sterile sites: a global systematic review","volume":"152","author":"Hagedoorn","year":"2023","journal-title":"Epidemiol Infect"},{"key":"B5","doi-asserted-by":"publisher","DOI":"10.3390\/vaccines10020328","article-title":"Towards a four-component GMMA-based vaccine against Shigella","volume":"10","author":"Micoli","year":"2022","journal-title":"Vaccines (Basel)"},{"key":"B6","doi-asserted-by":"publisher","DOI":"10.1016\/s0140-6736(13)60844-2","article-title":"Burden and aetiology of diarrhoeal disease in infants and young children in developing countries (the Global Enteric Multicenter Study, GEMS): a prospective, case-control study","volume":"382","author":"Kotloff","year":"2013","journal-title":"Lancet"},{"key":"B7","doi-asserted-by":"publisher","DOI":"10.1016\/j.lanmic.2024.101064","article-title":"Epidemiology of Shigella species and serotypes in children: a retrospective substudy of the MAL-ED observational birth cohort study","volume":"6","author":"Rogawski McQuade","year":"2025","journal-title":"Lancet Microbe"},{"key":"B8","doi-asserted-by":"publisher","DOI":"10.1016\/j.ebiom.2025.105903","article-title":"Safety and immunogenicity of the invasive non-typhoidal Salmonella (iNTS)-GMMA vaccine: a first-in-human, randomised, dose escalation trial","volume":"119","author":"Hanumunthadu","year":"2025","journal-title":"EBioMedicine"},{"key":"B9","doi-asserted-by":"publisher","DOI":"10.1016\/S1473-3099(25)00730-3","article-title":"Safety and immunogenicity of a conjugate vaccine candidate against Salmonella enterica serovars Typhi and Paratyphi A in healthy adults in Europe: a phase 1 randomised controlled trial","volume":"26","author":"De Coster","year":"2026","journal-title":"Lancet Infect Dis"},{"key":"B10","doi-asserted-by":"publisher","DOI":"10.1038\/s41591-025-04003-z","article-title":"A combination typhoid and non-typhoidal Salmonella polysaccharide conjugate vaccine in healthy adults: a randomized, placebo-controlled phase 1 trial","volume":"31","author":"Chen","year":"2025","journal-title":"Nat Med"},{"key":"B11","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":"B12","doi-asserted-by":"publisher","DOI":"10.3390\/vaccines10091376","article-title":"The Shigella vaccines pipeline","volume":"10","author":"MacLennan","year":"2022","journal-title":"Vaccines (Basel)"},{"key":"B13","doi-asserted-by":"publisher","DOI":"10.1016\/j.vaccine.2009.12.050","article-title":"Age-related efficacy of Shigella O-specific polysaccharide conjugates in 1-4-year-old Israeli children","volume":"28","author":"Passwell","year":"2010","journal-title":"Vaccine"},{"key":"B14","doi-asserted-by":"publisher","DOI":"10.1016\/S0140-6736(96)06255-1","article-title":"Double-blind vaccine-controlled randomised efficacy trial of an investigational Shigella sonnei conjugate vaccine in young adults","volume":"349","author":"Cohen","year":"1997","journal-title":"Lancet"},{"key":"B15","doi-asserted-by":"publisher","DOI":"10.1128\/mSphere.00260-18","article-title":"A novel Shigella proteome microarray discriminates targets of human antibody reactivity following oral vaccination and experimental challenge","volume":"3","author":"Ndungo","year":"2018","journal-title":"mSphere"},{"key":"B16","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.1307228110","article-title":"Multiple antigen-presenting system (MAPS) to induce comprehensive B- and T-cell immunity","volume":"110","author":"Zhang","year":"2013","journal-title":"Proc Natl Acad Sci USA"},{"key":"B17","doi-asserted-by":"publisher","first-page":"196","DOI":"10.1080\/14760584.2023.2299384","article-title":"Multiple antigen presenting system (MAPS): state of the art and potential applications","volume":"23","author":"Malley","year":"2024","journal-title":"Expert Rev Vaccines"},{"key":"B18","doi-asserted-by":"publisher","DOI":"10.3390\/vaccines12101091","article-title":"Evaluation of a quadrivalent Shigella flexneri serotype 2a, 3a, 6, and Shigella sonnei O-specific polysaccharide and IpaB MAPS vaccine","volume":"12","author":"Boerth","year":"2024","journal-title":"Vaccines (Basel)"},{"key":"B19","doi-asserted-by":"publisher","DOI":"10.1128\/mbio.03611-22","article-title":"A MAPS vaccine induces multipronged systemic and tissue-resident cellular responses and protects mice against Mycobacterium tuberculosis","volume":"14","author":"O'Hara","year":"2023","journal-title":"mBio"},{"key":"B20","doi-asserted-by":"publisher","DOI":"10.3390\/vaccines11111671","article-title":"Induction of broad immunity against invasive Salmonella disease by a quadrivalent combination Salmonella MAPS vaccine targeting Salmonella enterica serovars Typhimurium, Enteritidis, Typhi, and Paratyphi A","volume":"11","author":"Boerth","year":"2023","journal-title":"Vaccines (Basel)"},{"key":"B21","doi-asserted-by":"publisher","DOI":"10.1128\/mbio.03790-21","article-title":"Carrier proteins facilitate the generation of antipolysaccharide immunity via multiple mechanisms","volume":"13","author":"Zhang","year":"2022","journal-title":"MBio"},{"key":"B22","doi-asserted-by":"publisher","DOI":"10.3390\/vaccines11010091","article-title":"A bivalent MAPS vaccine induces protective antibody responses against Salmonella Typhi and Paratyphi A","volume":"11","author":"Zhang","year":"2022","journal-title":"Vaccines (Basel)"},{"key":"B23","doi-asserted-by":"publisher","DOI":"10.1016\/j.vaccine.2022.05.079","article-title":"Phase 1\/2 study of a novel 24-valent pneumococcal vaccine in healthy adults aged 18 to 64 years and in older adults aged 65 to 85 years","volume":"40","author":"Chichili","year":"2022","journal-title":"Vaccine"},{"key":"B24","article-title":"MAPS vaccine against Salmonella enterica serovars Typhimurium and Enteritidis","author":"Roy","year":"2021"},{"key":"B25","article-title":"Novel multivalent vaccine for Gram-negative bacterial pathogens, including multiple antibiotic-resistant strains","author":"Cross","year":"2019"},{"key":"B26","doi-asserted-by":"publisher","DOI":"10.1128\/mBio.01949-18","article-title":"Protection against Staphylococcus aureus colonization and infection by B- and T-cell-mediated mechanisms","volume":"9","author":"Zhang","year":"2018","journal-title":"MBio"},{"key":"B27","doi-asserted-by":"publisher","first-page":"158","DOI":"10.1038\/s41541-021-00418-0","article-title":"World in motion\" - emulsion adjuvants rising to meet the pandemic challenges","volume":"6","author":"O'Hagan","year":"2021","journal-title":"NPJ Vaccines"},{"key":"B28","doi-asserted-by":"publisher","DOI":"10.1016\/j.vaccine.2011.01.011","article-title":"Adjuvant system AS03 containing alpha-tocopherol modulates innate immune response and leads to improved adaptive immunity","volume":"29","author":"Morel","year":"2011","journal-title":"Vaccine"},{"key":"B29","doi-asserted-by":"publisher","first-page":"196","DOI":"10.1038\/ni758","article-title":"Small anti-viral compounds activate immune cells via the TLR7 MyD88-dependent signaling pathway","volume":"3","author":"Hemmi","year":"2002","journal-title":"Nat Immunol"},{"key":"B30","doi-asserted-by":"publisher","DOI":"10.3389\/fimmu.2022.836274","article-title":"R848 adjuvant laden with self-assembled nanoparticle-based mRNA vaccine elicits protective immunity against H5N1 in mice","volume":"13","author":"Zhuang","year":"2022","journal-title":"Front Immunol"},{"key":"B31","doi-asserted-by":"publisher","DOI":"10.3390\/vaccines10040494","article-title":"Analysis of R848 as an adjuvant to improve inactivated influenza vaccine immunogenicity in elderly nonhuman primates","volume":"10","author":"Crofts","year":"2022","journal-title":"Vaccines (Basel)"},{"key":"B32","doi-asserted-by":"publisher","first-page":"16860","DOI":"10.1038\/s41598-022-20346-w","article-title":"Development of a TLR7\/8 agonist adjuvant formulation to overcome early life hyporesponsiveness to DTaP vaccination","volume":"12","author":"Dowling","year":"2022","journal-title":"Sci Rep"},{"key":"B33","doi-asserted-by":"publisher","DOI":"10.1021\/acs.nanolett.5c03021","article-title":"A synthetic liposome nanoparticle vaccine platform for broad-spectrum vaccine design","volume":"25","author":"Zhang","year":"2025","journal-title":"Nano Lett"},{"key":"B34","doi-asserted-by":"publisher","first-page":"795","DOI":"10.1016\/j.addr.2007.12.004","article-title":"TLR9 as a key receptor for the recognition of DNA","volume":"60","author":"Kumagai","year":"2008","journal-title":"Adv Drug Delivery Rev"},{"key":"B35","doi-asserted-by":"publisher","DOI":"10.1080\/21645515.2022.2136912","article-title":"Immunogenicity and safety of a booster dose of the hepatitis B vaccine HepB-CpG (HEPLISAV-B(R)) compared with HepB-Eng (Engerix-B(R)) and HepB-AS04 (Fendrix(R)) in adults receiving hemodialysis who previously received hepatitis B vaccination and are not seroprotected: results of a randomized, multicenter phase 3 study","volume":"18","author":"Girndt","year":"2022","journal-title":"Hum Vaccines Immunotherapeutics"},{"key":"B36","doi-asserted-by":"publisher","DOI":"10.1016\/S2214-109X(24)00092-5","article-title":"Facilitating the development of urgently required combination vaccines","volume":"12","author":"Hausdorff","year":"2024","journal-title":"Lancet Glob Health"},{"key":"B37","doi-asserted-by":"publisher","first-page":"393","DOI":"10.1093\/cid\/civ295","article-title":"Safety and immunogenicity of a Vi polysaccharide-tetanus toxoid conjugate vaccine (Typbar-TCV) in healthy infants, children, and adults in typhoid endemic areas: a multicenter, 2-cohort, open-label, double-blind, randomized controlled phase 3 study","volume":"61","author":"Mohan","year":"2015","journal-title":"Clin Infect Dis"},{"key":"B38","doi-asserted-by":"publisher","DOI":"10.1172\/JCI33998","article-title":"The neglected role of antibody in protection against bacteremia caused by nontyphoidal strains of Salmonella in African children","volume":"118","author":"MacLennan","year":"2008","journal-title":"J Clin Invest"},{"key":"B39","doi-asserted-by":"publisher","DOI":"10.1016\/S1473-3099(18)30475-4","article-title":"Morbidity and mortality due to shigella and enterotoxigenic Escherichia coli diarrhoea: the Global Burden of Disease Study 1990-2016","volume":"18","author":"Khalil","year":"2018","journal-title":"Lancet Infect Dis"},{"key":"B40","doi-asserted-by":"publisher","DOI":"10.1016\/S0140-6736(24)01494-6","article-title":"5-year vaccine protection following a single dose of Vi-tetanus toxoid conjugate vaccine in Bangladeshi children (TyVOID): a cluster randomised trial","volume":"404","author":"Qadri","year":"2024","journal-title":"Lancet"},{"key":"B41","doi-asserted-by":"crossref","DOI":"10.2139\/ssrn.6327745","article-title":"Eight-year vaccine protection following a single dose of VI-tetanus toxoid conjugate vaccine in Nepali children: extended follow-up of the TyVAC Nepal randomised controlled trial","volume-title":"Ssrn","author":"Pant","year":"2026"},{"key":"B42","doi-asserted-by":"publisher","DOI":"10.1016\/s0140-6736(23)02031-7","article-title":"Efficacy of typhoid conjugate vaccine: final analysis of a 4-year, phase 3, randomised controlled trial in Malawian children","volume":"403","author":"Patel","year":"2024","journal-title":"Lancet"},{"key":"B43","doi-asserted-by":"publisher","DOI":"10.1016\/j.vaccine.2024.02.010","article-title":"Immune responses to typhoid conjugate vaccine in a two dose schedule among Nepalese children <2 years of age","volume":"42","author":"Bijukchhe","year":"2024","journal-title":"Vaccine"},{"key":"B44","doi-asserted-by":"publisher","DOI":"10.1016\/j.eclinm.2025.103100","article-title":"Immunogenicity and reactogenicity of a booster dose of a typhoid conjugate vaccine (TCV) in Malawian pre-school children","volume":"81","author":"Nampota-Nkomba","year":"2025","journal-title":"EClinicalMedicine"},{"key":"B45","doi-asserted-by":"publisher","first-page":"283","DOI":"10.1038\/s41392-023-01557-7","article-title":"Vaccine adjuvants: mechanisms and platforms","volume":"8","author":"Zhao","year":"2023","journal-title":"Signal Transduct Target Ther"},{"key":"B46","doi-asserted-by":"publisher","DOI":"10.1016\/S1473-3099(13)70238-X","article-title":"Pandemic influenza A H1N1 vaccines and narcolepsy: vaccine safety surveillance in action","volume":"14","author":"Barker","year":"2014","journal-title":"Lancet Infect Dis"},{"key":"B47","doi-asserted-by":"publisher","DOI":"10.3389\/fimmu.2017.01760","article-title":"AS03- and MF59-adjuvanted influenza vaccines in children","volume":"8","author":"Wilkins","year":"2017","journal-title":"Front Immunol"},{"key":"B48","doi-asserted-by":"publisher","DOI":"10.1126\/sciimmunol.adi8039","article-title":"AS03 adjuvant enhances the magnitude, persistence, and clonal breadth of memory B cell responses to a plant-based COVID-19 vaccine in humans","volume":"9","author":"Grigoryan","year":"2024","journal-title":"Sci Immunol"},{"key":"B49","doi-asserted-by":"publisher","DOI":"10.1093\/infdis\/jiaf600","article-title":"Safety and immunogenicity of a Klebsiella pneumoniae tetravalent bioconjugate vaccine (Kleb4V) administered to healthy adults: a first time in human phase I\/II randomised and controlled study","volume":"233","author":"Alaimo","year":"2025","journal-title":"J Infect Dis"},{"key":"B50","doi-asserted-by":"publisher","DOI":"10.1128\/jcm.26.4.719-725.1988","article-title":"Application of optical properties of the Vi capsular polysaccharide for quantitation of the Vi antigen in vaccines for typhoid fever","volume":"26","author":"Stone","year":"1988","journal-title":"J Clin Microbiol"},{"key":"B51","doi-asserted-by":"publisher","DOI":"10.1016\/s0021-9258(18)71120-4","article-title":"The determination of sugar in blood and spinal fluid with anthrone reagent","volume":"212","author":"Roe","year":"1955","journal-title":"J Biol Chem"},{"key":"B52","doi-asserted-by":"publisher","DOI":"10.1128\/iai.64.7.2709-2715.1996","article-title":"Synthesis, characterization, and immunological properties in mice of conjugates composed of detoxified lipopolysaccharide of Salmonella paratyphi A bound to tetanus toxoid with emphasis on the role of O acetyls","volume":"64","author":"Konadu","year":"1996","journal-title":"Infect Immun"},{"key":"B53","doi-asserted-by":"publisher","DOI":"10.1016\/j.vaccine.2012.03.039","article-title":"A bivalent vaccine to protect against Streptococcus pneumoniae and Salmonella typhi","volume":"30","author":"Lu","year":"2012","journal-title":"Vaccine"},{"key":"B54","doi-asserted-by":"publisher","DOI":"10.1128\/mSphere.00146-18","article-title":"Development, interlaboratory evaluations, and application of a simple, high-throughput Shigella serum bactericidal assay","volume":"3","author":"Nahm","year":"2018","journal-title":"mSphere"}],"container-title":["Frontiers in Immunology"],"original-title":[],"link":[{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fimmu.2026.1886839\/full","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,7,27]],"date-time":"2026-07-27T05:41:13Z","timestamp":1785130873000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fimmu.2026.1886839\/full"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,7,27]]},"references-count":54,"alternative-id":["10.3389\/fimmu.2026.1886839"],"URL":"https:\/\/doi.org\/10.3389\/fimmu.2026.1886839","relation":{},"ISSN":["1664-3224"],"issn-type":[{"value":"1664-3224","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,7,27]]},"article-number":"1886839"}}