{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,2,11]],"date-time":"2026-02-11T02:46:10Z","timestamp":1770777970818,"version":"3.50.0"},"reference-count":36,"publisher":"Oxford University Press (OUP)","issue":"2","license":[{"start":{"date-parts":[[2020,7,1]],"date-time":"2020-07-01T00:00:00Z","timestamp":1593561600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/academic.oup.com\/pages\/standard-publication-reuse-rights"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2020,7,15]]},"abstract":"<jats:title>Abstract<\/jats:title>\n               <jats:p>Pathogenic Salmonella serovars produce clinical manifestations ranging from systemic infection typhoid to invasive nontyphoidal Salmonella disease in humans. These serovars share a high degree of homology at the genome and the proteome level. However, whether infection or immunization with one serovar provides protection against other serovars has not been well studied. We show in this study that immunization of mice with live typhoidal serovar, Salmonella Typhi, generates cross-reactive immune responses, which provide far greater resistance against challenge with nontyphoidal serovar Salmonella Enteritidis than with another nontyphoidal serovar, Salmonella Typhimurium. Splenic T cells from these immunized mice produced similar levels of IL-2 and IFN-\u03b3 upon ex vivo stimulation with Ags prepared from S. Enteritidis and S. Typhimurium. In contrast, Abs against S. Typhi interacted with live intact S. Enteritidis but did not bind intact S. Typhimurium. These pathogen-reactive Abs were largely directed against oligosaccharide (O)-antigenic determinant of LPS that S. Typhi shares with S. Enteritidis. Abs against the O determinant, which S. Typhi shares with S. Typhimurium, were present in the sera of immunized mice but did not bind live intact Salmonella because of surface inaccessibility of this determinant. Similar accessibility-regulated interaction was seen with Abs generated against S. Typhimurium and S. Enteritidis. Our results suggest that the ability of protective Abs elicited with one Salmonella serovar to engage with and consequently provide protection against another Salmonella serovar is determined by the accessibility of shared O Ags. These findings have significant and broader implications for immunity and vaccine development against pathogenic Salmonellae.<\/jats:p>","DOI":"10.4049\/jimmunol.1900624","type":"journal-article","created":{"date-parts":[[2020,6,15]],"date-time":"2020-06-15T19:45:14Z","timestamp":1592250314000},"page":"438-446","source":"Crossref","is-referenced-by-count":5,"title":["Accessibility of O Antigens Shared between <i>Salmonella<\/i> Serovars Determines Antibody-Mediated Cross-Protection"],"prefix":"10.1093","volume":"205","author":[{"given":"Anees","family":"Ahmed","sequence":"first","affiliation":[{"name":"Hybridoma Laboratory, National Institute of Immunology , New Delhi 110067 ,","place":["India"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Ajay Suresh","family":"Akhade","sequence":"additional","affiliation":[{"name":"Hybridoma Laboratory, National Institute of Immunology , New Delhi 110067 ,","place":["India"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Ayub","family":"Qadri","sequence":"additional","affiliation":[{"name":"Hybridoma Laboratory, National Institute of Immunology , New Delhi 110067 ,","place":["India"]}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"286","published-online":{"date-parts":[[2020,7,15]]},"reference":[{"key":"2025030417504221100_r1","doi-asserted-by":"crossref","first-page":"317","DOI":"10.1146\/annurev-micro-091313-103739","article-title":"Salmonella enterica serovar Typhi and the pathogenesis of typhoid fever","volume":"68","author":"Dougan","year":"2014","journal-title":"Annu. Rev. Microbiol."},{"key":"2025030417504221100_r2","first-page":"346","article-title":"The global burden of typhoid fever","volume":"82","author":"Crump","year":"2004","journal-title":"Bull. World Health Organ."},{"key":"2025030417504221100_r3","doi-asserted-by":"crossref","first-page":"882","DOI":"10.1086\/650733","article-title":"The global burden of nontyphoidal Salmonella gastroenteritis","volume":"50","author":"Majowicz","year":"2010","journal-title":"Clin. Infect. Dis."},{"key":"2025030417504221100_r4","doi-asserted-by":"crossref","first-page":"2907","DOI":"10.1016\/j.vaccine.2016.03.072","article-title":"Nontyphoidal salmonella disease: current status of vaccine research and development","volume":"34","author":"Tennant","year":"2016","journal-title":"Vaccine"},{"key":"2025030417504221100_r5","doi-asserted-by":"crossref","first-page":"94","DOI":"10.1016\/S0966-842X(01)02293-4","article-title":"Comparative genomics of closely related salmonellae","volume":"10","author":"Edwards","year":"2002","journal-title":"Trends Microbiol."},{"key":"2025030417504221100_r6","doi-asserted-by":"crossref","first-page":"553","DOI":"10.1128\/JB.185.2.553-563.2003","article-title":"Genomic comparison of Salmonella enterica serovars and Salmonella bongori by use of an S. enterica serovar typhimurium DNA microarray","volume":"185","author":"Chan","year":"2003","journal-title":"J. Bacteriol."},{"key":"2025030417504221100_r7","doi-asserted-by":"crossref","first-page":"4579","DOI":"10.1128\/IAI.66.10.4579-4587.1998","article-title":"Evolution of host adaptation in Salmonella enterica","volume":"66","author":"B\u00e4umler","year":"1998","journal-title":"Infect. Immun."},{"key":"2025030417504221100_r8","doi-asserted-by":"crossref","first-page":"746","DOI":"10.1128\/CVI.00258-16","article-title":"Animal models for salmonellosis: applications in vaccine research","volume":"23","author":"Higginson","year":"2016","journal-title":"Clin. Vaccine Immunol."},{"key":"2025030417504221100_r9","doi-asserted-by":"crossref","first-page":"1806","DOI":"10.1128\/IAI.01369-10","article-title":"How to become a top model: impact of animal experimentation on human Salmonella disease research","volume":"79","author":"Tsolis","year":"2011","journal-title":"Infect. Immun."},{"key":"2025030417504221100_r10","doi-asserted-by":"crossref","first-page":"3344","DOI":"10.1128\/IAI.68.6.3344-3348.2000","article-title":"Antibody is required for protection against virulent but not attenuated Salmonella enterica serovar typhimurium","volume":"68","author":"McSorley","year":"2000","journal-title":"Infect. Immun."},{"key":"2025030417504221100_r11","doi-asserted-by":"crossref","first-page":"4679","DOI":"10.1128\/iai.60.11.4679-4686.1992","article-title":"Protection of mice against Salmonella typhimurium with an O-specific polysaccharide-protein conjugate vaccine","volume":"60","author":"Watson","year":"1992","journal-title":"Infect. Immun."},{"key":"2025030417504221100_r12","doi-asserted-by":"crossref","first-page":"3722","DOI":"10.1128\/IAI.00547-15","article-title":"Monoclonal antibodies of a diverse isotype induced by an O-antigen glycoconjugate vaccine mediate in vitro and in vivo killing of African invasive nontyphoidal Salmonella","volume":"83","author":"Goh","year":"2015","journal-title":"Infect. Immun."},{"key":"2025030417504221100_r13","doi-asserted-by":"crossref","first-page":"1566","DOI":"10.1128\/iai.65.4.1566-1569.1997","article-title":"Salmonella typhimurium aroA, htrA, and aroD htrA mutants cause progressive infections in athymic (nu\/nu) BALB\/c mice","volume":"65","author":"Sinha","year":"1997","journal-title":"Infect. Immun."},{"key":"2025030417504221100_r14","doi-asserted-by":"crossref","first-page":"3321","DOI":"10.4049\/jimmunol.156.9.3321","article-title":"Salmonella typhimurium aroA- infection in gene-targeted immunodeficient mice: major role of CD4+ TCR-alpha beta cells and IFN-gamma in bacterial clearance independent of intracellular location","volume":"156","author":"Hess","year":"1996","journal-title":"J. Immunol."},{"key":"2025030417504221100_r15","doi-asserted-by":"crossref","first-page":"1002","DOI":"10.1128\/JB.180.4.1002-1007.1998","article-title":"Relationships among the O-antigen gene clusters of Salmonella enterica groups B, D1, D2, and D3","volume":"180","author":"Curd","year":"1998","journal-title":"J. Bacteriol."},{"key":"2025030417504221100_r16","doi-asserted-by":"crossref","first-page":"1588","DOI":"10.3891\/acta.chem.scand.23-1588","article-title":"Structural studies on the O-specific side chains of the cell wall lipopolysaccharides from Salmonella typhi and S. enteritidis","volume":"23","author":"Hellerqvist","year":"1969","journal-title":"Acta Chem. Scand."},{"key":"2025030417504221100_r17","doi-asserted-by":"crossref","first-page":"2292","DOI":"10.1128\/jcm.26.11.2292-2296.1988","article-title":"Monoclonal antibodies delineate multiple epitopes on the O antigens of Salmonella typhi lipopolysaccharide","volume":"26","author":"Qadri","year":"1988","journal-title":"J. Clin. Microbiol."},{"key":"2025030417504221100_r18","doi-asserted-by":"crossref","first-page":"2465","DOI":"10.1128\/JCM.38.7.2465-2467.2000","article-title":"Salmonella nomenclature","volume":"38","author":"Brenner","year":"2000","journal-title":"J. Clin. Microbiol."},{"key":"2025030417504221100_r19","doi-asserted-by":"crossref","first-page":"327","DOI":"10.1038\/ni.2548","article-title":"Intracellular antibody-bound pathogens stimulate immune signaling via the Fc receptor TRIM21","volume":"14","author":"McEwan","year":"2013","journal-title":"Nat. Immunol."},{"key":"2025030417504221100_r20","first-page":"131","article-title":"Antibody- and TRIM21-dependent intracellular restriction of Salmonella enterica","volume":"72","author":"Rakebrandt","year":"2014","journal-title":"Pathog. Dis."},{"key":"2025030417504221100_r21","doi-asserted-by":"crossref","DOI":"10.1371\/journal.ppat.1000567","article-title":"O-antigen delays lipopolysaccharide recognition and impairs antibacterial host defense in murine intestinal epithelial cells","volume":"5","author":"Duerr","year":"2009","journal-title":"PLoS Pathog."},{"key":"2025030417504221100_r22","doi-asserted-by":"crossref","first-page":"490","DOI":"10.1128\/iai.32.2.490-496.1981","article-title":"Artificial Salmonella vaccines: Salmonella typhimurium O-antigen-specific oligosaccharide-protein conjugates elicit protective antibodies in rabbits and mice","volume":"32","author":"Svenson","year":"1981","journal-title":"Infect. Immun."},{"key":"2025030417504221100_r23","doi-asserted-by":"crossref","first-page":"996","DOI":"10.1128\/IAI.03079-14","article-title":"Design of glycoconjugate vaccines against invasive African Salmonella enterica serovar Typhimurium","volume":"83","author":"Rondini","year":"2015","journal-title":"Infect. Immun."},{"key":"2025030417504221100_r24","doi-asserted-by":"crossref","first-page":"4240","DOI":"10.1128\/IAI.05484-11","article-title":"Salmonella enterica serovar enteritidis core O polysaccharide conjugated to H:g,m flagellin as a candidate vaccine for protection against invasive infection with S. enteritidis","volume":"79","author":"Simon","year":"2011","journal-title":"Infect. Immun."},{"key":"2025030417504221100_r25","doi-asserted-by":"crossref","first-page":"10428","DOI":"10.1073\/pnas.1807655115","article-title":"Comparative immunogenicity and efficacy of equivalent outer membrane vesicle and glycoconjugate vaccines against nontyphoidal Salmonella","volume":"115","author":"Micoli","year":"2018","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"2025030417504221100_r26","doi-asserted-by":"crossref","first-page":"168","DOI":"10.3389\/fimmu.2017.00168","article-title":"Immunogenicity of a bivalent adjuvanted glycoconjugate vaccine against Salmonella typhimurium and Salmonella enteritidis","volume":"8","author":"Fiorino","year":"2017","journal-title":"Front. Immunol."},{"key":"2025030417504221100_r27","doi-asserted-by":"crossref","first-page":"851","DOI":"10.1038\/s41467-020-14655-9","article-title":"Outer membrane protein size and LPS O-antigen define protective antibody targeting to the Salmonella surface","volume":"11","author":"Dom\u00ednguez-Medina","year":"2020","journal-title":"Nat. Commun."},{"key":"2025030417504221100_r28","doi-asserted-by":"crossref","first-page":"1478","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":"2025030417504221100_r29","doi-asserted-by":"crossref","first-page":"443","DOI":"10.1586\/eri.13.27","article-title":"Invasive nontyphoidal Salmonella disease in Africa: current status","volume":"11","author":"MacLennan","year":"2013","journal-title":"Expert Rev. Anti Infect. Ther."},{"key":"2025030417504221100_r30","doi-asserted-by":"crossref","first-page":"825","DOI":"10.1128\/CVI.00058-12","article-title":"Live oral typhoid vaccine Ty21a induces cross-reactive humoral immune responses against Salmonella enterica serovar Paratyphi A and S. Paratyphi B in humans","volume":"19","author":"Wahid","year":"2012","journal-title":"Clin. Vaccine Immunol."},{"key":"2025030417504221100_r31","doi-asserted-by":"crossref","first-page":"2023","DOI":"10.1128\/iai.60.5.2023-2029.1992","article-title":"Indirect measurement of intestinal immune responses to an orally administered attenuated bacterial vaccine","volume":"60","author":"Forrest","year":"1992","journal-title":"Infect. Immun."},{"key":"2025030417504221100_r32","doi-asserted-by":"crossref","first-page":"427","DOI":"10.1128\/CVI.00786-13","article-title":"Live oral Salmonella enterica serovar Typhi vaccines Ty21a and CVD 909 induce opsonophagocytic functional antibodies in humans that cross-react with S. Paratyphi A and S. Paratyphi B","volume":"21","author":"Wahid","year":"2014","journal-title":"Clin. Vaccine Immunol."},{"key":"2025030417504221100_r33","doi-asserted-by":"crossref","first-page":"1055","DOI":"10.1016\/0140-6736(91)91910-M","article-title":"Oral immunisation against typhoid fever in Indonesia with Ty21a vaccine","volume":"338","author":"Simanjuntak","year":"1991","journal-title":"Lancet"},{"key":"2025030417504221100_r34","doi-asserted-by":"crossref","first-page":"451","DOI":"10.1016\/j.vaccine.2014.11.030","article-title":"Specific and cross-reactive immune response to oral Salmonella Typhi Ty21a and parenteral Vi capsular polysaccharide typhoid vaccines administered concomitantly","volume":"33","author":"Pakkanen","year":"2015","journal-title":"Vaccine"},{"key":"2025030417504221100_r35","doi-asserted-by":"crossref","first-page":"7238","DOI":"10.1016\/j.vaccine.2012.10.002","article-title":"Live oral typhoid vaccine Salmonella Typhi Ty21a - a surrogate vaccine against non-typhoid salmonella?","volume":"30","author":"Kantele","year":"2012","journal-title":"Vaccine"},{"key":"2025030417504221100_r36","doi-asserted-by":"crossref","first-page":"eaau6849","DOI":"10.1126\/sciadv.aau6849","article-title":"Nonspecific effects of oral vaccination with live-attenuated Salmonella typhi strain Ty21a","volume":"5","author":"Pennington","year":"2019","journal-title":"Sci. Adv."}],"container-title":["The Journal of Immunology"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/academic.oup.com\/jimmunol\/article-pdf\/205\/2\/438\/61878879\/ji1900624.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"syndication"},{"URL":"https:\/\/academic.oup.com\/jimmunol\/article-pdf\/205\/2\/438\/61878879\/ji1900624.pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,3,4]],"date-time":"2025-03-04T18:00:32Z","timestamp":1741111232000},"score":1,"resource":{"primary":{"URL":"https:\/\/academic.oup.com\/jimmunol\/article\/205\/2\/438\/7930756"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2020,7]]},"references-count":36,"journal-issue":{"issue":"2","published-print":{"date-parts":[[2020,7,15]]}},"URL":"https:\/\/doi.org\/10.4049\/jimmunol.1900624","relation":{},"ISSN":["0022-1767","1550-6606"],"issn-type":[{"value":"0022-1767","type":"print"},{"value":"1550-6606","type":"electronic"}],"subject":[],"published-other":{"date-parts":[[2020,7]]},"published":{"date-parts":[[2020,7]]}}}