{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,17]],"date-time":"2026-09-17T13:34:09Z","timestamp":1789652049224,"version":"4.0.0"},"reference-count":45,"publisher":"Wiley","issue":"8","license":[{"start":{"date-parts":[[2015,8,14]],"date-time":"2015-08-14T00:00:00Z","timestamp":1439510400000},"content-version":"vor","delay-in-days":13,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"funder":[{"name":"a scientific and technological research project of Chongqing","award":["cstc2012gg-yyjs10057"],"award-info":[{"award-number":["cstc2012gg-yyjs10057"]}]},{"name":"a translational research grant of Third Military Medical University"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Microbiology and Immunology"],"published-print":{"date-parts":[[2015,8]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:sec><jats:label\/><jats:p>The global epidemic features of enteric fever have changed greatly in recent years. The incidence of enteric fever caused by <jats:italic>Salmonella<\/jats:italic> <jats:italic>enterica<\/jats:italic> serovar Paratyphi A has progressively increased. In some areas of Asia, infections with <jats:italic>S<\/jats:italic>. Paratyphi A have exceeded those with <jats:italic>S<\/jats:italic>. Typhi, resulting in <jats:italic>S<\/jats:italic>. Paratyphi A becoming the main causative agent of enteric fever. However, two currently licensed typhoid vaccines do not confer adequate cross\u2010protection against <jats:italic>S<\/jats:italic>. Paratyphi A infection. Therefore, development of specific vaccines against enteric fever caused by <jats:italic>S<\/jats:italic>. Paratyphi A is urgently needed. In the present study, an attenuated strain was constructed by double deletion of the <jats:italic>htrA<\/jats:italic> and <jats:italic>yncD<\/jats:italic> genes in a wild\u2010type strain of <jats:italic>S<\/jats:italic>. Paratyphi A and its safety and immunogenicity assessed. In a mouse model, the 50% lethal dose of the double deletion mutant and the wild\u2010type strain were 3.0\u2009\u00d7\u200910<jats:sup>8<\/jats:sup> CFU and 1.9\u2009\u00d7\u200910<jats:sup>3<\/jats:sup> CFU, respectively, suggesting that the double deletion resulted in remarkably decreased bacterial virulence. Bacterial colonization of the double deletion mutant in the livers and spleens of infected mice was strikingly less than that of the wild\u2010type strain. A single nasal administration of the attenuated vaccine candidate elicited high concentrations of anti\u2010LPS and anti\u2010flagellin IgG in a mouse model and protected immunized mice against lethal challenge with the wild\u2010type strain. Thus, our findings suggest that the attenuated vaccine strain is a promising candidate worthy of further evaluation both as a human enteric fever vaccine and as a vaccine delivery vector for heterologous antigens.<\/jats:p><\/jats:sec>","DOI":"10.1111\/1348-0421.12276","type":"journal-article","created":{"date-parts":[[2015,6,18]],"date-time":"2015-06-18T08:05:31Z","timestamp":1434614731000},"page":"443-451","source":"Crossref","is-referenced-by-count":14,"title":["Construction of an attenuated <i>Salmonella enterica<\/i> serovar Paratyphi A vaccine strain harboring defined mutations in <i>htrA<\/i> and <i>yncD<\/i>"],"prefix":"10.1111","volume":"59","author":[{"given":"Chunyue","family":"Zhu","sequence":"first","affiliation":[{"name":"Department of Microbiology Third Military Medical University Chongqing 400038 China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kun","family":"Xiong","sequence":"additional","affiliation":[{"name":"Department of Microbiology Third Military Medical University Chongqing 400038 China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zhijin","family":"Chen","sequence":"additional","affiliation":[{"name":"Department of Microbiology Third Military Medical University Chongqing 400038 China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xiaomei","family":"Hu","sequence":"additional","affiliation":[{"name":"Department of Microbiology Third Military Medical University Chongqing 400038 China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jianhua","family":"Li","sequence":"additional","affiliation":[{"name":"Department of Microbiology Third Military Medical University Chongqing 400038 China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yiran","family":"Wang","sequence":"additional","affiliation":[{"name":"Department of Microbiology Third Military Medical University Chongqing 400038 China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xiancai","family":"Rao","sequence":"additional","affiliation":[{"name":"Department of Microbiology Third Military Medical University Chongqing 400038 China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yanguang","family":"Cong","sequence":"additional","affiliation":[{"name":"Department of Microbiology Third Military Medical University Chongqing 400038 China"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2015,8,14]]},"reference":[{"key":"e_1_2_8_2_1","doi-asserted-by":"publisher","DOI":"10.1086\/649541"},{"key":"e_1_2_8_3_1","first-page":"346","article-title":"The global burden of typhoid fever","volume":"82","author":"Crump J.A.","year":"2004","journal-title":"Bull World Health Organ"},{"key":"e_1_2_8_4_1","doi-asserted-by":"publisher","DOI":"10.3201\/eid1111.050168"},{"key":"e_1_2_8_5_1","doi-asserted-by":"publisher","DOI":"10.1097\/QCO.0b013e32833c7ca1"},{"key":"e_1_2_8_6_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1708-8305.2008.00237.x"},{"key":"e_1_2_8_7_1","doi-asserted-by":"publisher","DOI":"10.1586\/14760584.2013.825450"},{"key":"e_1_2_8_8_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0140-6736(13)62708-7"},{"key":"e_1_2_8_9_1","doi-asserted-by":"publisher","DOI":"10.4161\/hv.29054"},{"key":"e_1_2_8_10_1","doi-asserted-by":"publisher","DOI":"10.1136\/bmj.316.7125.110"},{"key":"e_1_2_8_11_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.vaccine.2007.08.027"},{"key":"e_1_2_8_12_1","doi-asserted-by":"publisher","DOI":"10.1016\/S2214-109X(14)70009-9"},{"key":"e_1_2_8_13_1","doi-asserted-by":"publisher","DOI":"10.1586\/erv.10.43"},{"key":"e_1_2_8_14_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.vaccine.2005.07.111"},{"key":"e_1_2_8_15_1","doi-asserted-by":"publisher","DOI":"10.1002\/jlb.67.4.457"},{"key":"e_1_2_8_16_1","doi-asserted-by":"publisher","DOI":"10.1038\/nm0103-99"},{"key":"e_1_2_8_17_1","doi-asserted-by":"publisher","DOI":"10.2174\/1381612811319060003"},{"key":"e_1_2_8_18_1","doi-asserted-by":"publisher","DOI":"10.1038\/nrm3065"},{"key":"e_1_2_8_19_1","doi-asserted-by":"publisher","DOI":"10.1016\/S1097-2765(02)00658-5"},{"key":"e_1_2_8_20_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1365-2958.1991.tb02122.x"},{"key":"e_1_2_8_21_1","doi-asserted-by":"publisher","DOI":"10.1016\/0882-4010(92)90117-7"},{"key":"e_1_2_8_22_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.vaccine.2009.06.060"},{"key":"e_1_2_8_23_1","first-page":"280","article-title":"Evaluation of vaccine candidate potential of \u0394aroA, \u0394htrA and \u0394aroA\u0394htrA mutants of Salmonella \n                  enterica subspecies enterica serovar Abortusequi in guinea pigs","volume":"51","author":"Singh B.R.","year":"2013","journal-title":"Indian J Exp Biol"},{"key":"e_1_2_8_24_1","doi-asserted-by":"publisher","DOI":"10.1086\/518135"},{"key":"e_1_2_8_25_1","doi-asserted-by":"publisher","DOI":"10.1128\/IAI.67.2.700-707.1999"},{"key":"e_1_2_8_26_1","doi-asserted-by":"publisher","DOI":"10.1128\/AEM.01457-12"},{"key":"e_1_2_8_27_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1574-6968.2011.02481.x"},{"key":"e_1_2_8_28_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0092-1157(80)80049-7"},{"key":"e_1_2_8_29_1","doi-asserted-by":"publisher","DOI":"10.1128\/IAI.69.8.4734-4741.2001"},{"key":"e_1_2_8_30_1","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pntd.0001373"},{"key":"e_1_2_8_31_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.vaccine.2010.03.019"},{"key":"e_1_2_8_32_1","doi-asserted-by":"publisher","DOI":"10.1007\/s11274-011-0786-3"},{"key":"e_1_2_8_33_1","doi-asserted-by":"publisher","DOI":"10.1046\/j.1365-2958.1997.5601928.x"},{"key":"e_1_2_8_34_1","doi-asserted-by":"publisher","DOI":"10.1128\/jb.171.5.2689-2696.1989"},{"key":"e_1_2_8_35_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1348-0421.1998.tb01962.x"},{"key":"e_1_2_8_36_1","doi-asserted-by":"publisher","DOI":"10.1038\/cmi.2008.11"},{"key":"e_1_2_8_37_1","doi-asserted-by":"publisher","DOI":"10.1093\/infdis\/131.5.553"},{"key":"e_1_2_8_38_1","doi-asserted-by":"publisher","DOI":"10.1093\/infdis\/145.3.292"},{"key":"e_1_2_8_39_1","doi-asserted-by":"publisher","DOI":"10.1016\/0140-6736(90)92266-K"},{"key":"e_1_2_8_40_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1365-2958.1996.tb02620.x"},{"key":"e_1_2_8_41_1","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.85.5.1576"},{"key":"e_1_2_8_42_1","doi-asserted-by":"publisher","DOI":"10.1128\/jb.171.3.1574-1584.1989"},{"key":"e_1_2_8_43_1","doi-asserted-by":"publisher","DOI":"10.1099\/mic.0.023754-0"},{"key":"e_1_2_8_44_1","doi-asserted-by":"publisher","DOI":"10.1016\/0882-4010(90)90023-J"},{"key":"e_1_2_8_45_1","doi-asserted-by":"crossref","first-page":"816","DOI":"10.1128\/iai.10.4.816-822.1974","article-title":"Growth of typhoid and paratyphoid bacilli in intravenously infected mice","volume":"10","author":"Carter P.B.","year":"1974","journal-title":"Infect Immun"},{"key":"e_1_2_8_46_1","doi-asserted-by":"publisher","DOI":"10.1016\/0264-410X(91)90218-U"}],"container-title":["Microbiology and Immunology"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/api.wiley.com\/onlinelibrary\/tdm\/v1\/articles\/10.1111%2F1348-0421.12276","content-type":"unspecified","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1111\/1348-0421.12276","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2023,10,5]],"date-time":"2023-10-05T00:27:14Z","timestamp":1696465634000},"score":1,"resource":{"primary":{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/10.1111\/1348-0421.12276"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2015,8]]},"references-count":45,"journal-issue":{"issue":"8","published-print":{"date-parts":[[2015,8]]}},"alternative-id":["10.1111\/1348-0421.12276"],"URL":"https:\/\/doi.org\/10.1111\/1348-0421.12276","archive":["Portico"],"relation":{},"ISSN":["0385-5600","1348-0421"],"issn-type":[{"value":"0385-5600","type":"print"},{"value":"1348-0421","type":"electronic"}],"subject":[],"published":{"date-parts":[[2015,8]]}}}