{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,6,22]],"date-time":"2026-06-22T15:24:51Z","timestamp":1782141891711,"version":"3.54.5"},"reference-count":50,"publisher":"Public Library of Science (PLoS)","issue":"9","license":[{"start":{"date-parts":[[2016,9,27]],"date-time":"2016-09-27T00:00:00Z","timestamp":1474934400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/publicdomain\/zero\/1.0\/"}],"content-domain":{"domain":["www.plosone.org"],"crossmark-restriction":false},"short-container-title":["PLoS ONE"],"DOI":"10.1371\/journal.pone.0163511","type":"journal-article","created":{"date-parts":[[2016,9,27]],"date-time":"2016-09-27T18:04:59Z","timestamp":1474999499000},"page":"e0163511","update-policy":"https:\/\/doi.org\/10.1371\/journal.pone.corrections_policy","source":"Crossref","is-referenced-by-count":21,"title":["Development of an Acid-Resistant Salmonella Typhi Ty21a Attenuated Vector For Improved Oral Vaccine Delivery"],"prefix":"10.1371","volume":"11","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-4954-2487","authenticated-orcid":false,"given":"Madushini N.","family":"Dharmasena","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Catherine M.","family":"Feuille","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Carly Elizabeth C.","family":"Starke","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Arvind A.","family":"Bhagwat","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Scott","family":"Stibitz","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Dennis J.","family":"Kopecko","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"340","published-online":{"date-parts":[[2016,9,27]]},"reference":[{"issue":"4","key":"ref1","doi-asserted-by":"crossref","first-page":"233","DOI":"10.1016\/j.ijmm.2008.09.003","article-title":"Genetic stability of vaccine strain <italic>Salmonella<\/italic> Typhi Ty21a over 25 years","volume":"299","author":"DJ Kopecko","year":"2009","journal-title":"International journal of medical microbiology: IJMM"},{"issue":"45","key":"ref2","doi-asserted-by":"crossref","first-page":"7848","DOI":"10.1016\/j.vaccine.2007.08.027","article-title":"Typhoid fever vaccines: systematic review and meta-analysis of randomised controlled trials","volume":"25","author":"A Fraser","year":"2007","journal-title":"Vaccine"},{"issue":"Suppl 2","key":"ref3","doi-asserted-by":"crossref","first-page":"S22","DOI":"10.1016\/S0264-410X(99)00231-5","article-title":"Duration of efficacy of Ty21a, attenuated <italic>Salmonella<\/italic> typhi live oral vaccine","volume":"17","author":"MM Levine","year":"1999","journal-title":"Vaccine"},{"issue":"2","key":"ref4","doi-asserted-by":"crossref","first-page":"91","DOI":"10.1038\/cmi.2008.11","article-title":"<italic>Salmonella<\/italic> typhi: from a human pathogen to a vaccine vector","volume":"5","author":"XL Zhang","year":"2008","journal-title":"Cellular & molecular immunology"},{"issue":"33","key":"ref5","doi-asserted-by":"crossref","first-page":"6167","DOI":"10.1016\/j.vaccine.2007.06.003","article-title":"Core-linked LPS expression of <italic>Shigella dysenteriae<\/italic> serotype 1 O-antigen in live <italic>Salmonella<\/italic> Typhi vaccine vector Ty21a: preclinical evidence of immunogenicity and protection","volume":"25","author":"DQ Xu","year":"2007","journal-title":"Vaccine"},{"issue":"8","key":"ref6","doi-asserted-by":"crossref","first-page":"4414","DOI":"10.1128\/IAI.70.8.4414-4423.2002","article-title":"Molecular cloning and characterization of genes for Shigella sonnei form I O polysaccharide: proposed biosynthetic pathway and stable expression in a live salmonella vaccine vector","volume":"70","author":"DQ Xu","year":"2002","journal-title":"Infection and immunity"},{"issue":"3","key":"ref7","doi-asserted-by":"crossref","first-page":"105","DOI":"10.1016\/j.ijmm.2013.01.001","article-title":"Stable expression of <italic>Shigella sonnei<\/italic> form I O-polysaccharide genes recombineered into the chromosome of live <italic>Salmonella<\/italic> oral vaccine vector Ty21a","volume":"303","author":"MN Dharmasena","year":"2013","journal-title":"International journal of medical microbiology: IJMM"},{"issue":"4","key":"ref8","doi-asserted-by":"crossref","first-page":"1475","DOI":"10.1128\/IAI.00828-08","article-title":"Anthrax protective antigen delivered by Salmonella enterica serovar Typhi Ty21a protects mice from a lethal anthrax spore challenge","volume":"77","author":"M Osorio","year":"2009","journal-title":"Infection and immunity"},{"issue":"10","key":"ref9","doi-asserted-by":"crossref","first-page":"1285","DOI":"10.1128\/CVI.00164-07","article-title":"<italic>Salmonella enterica<\/italic> serovar Typhi Ty21a expressing human papillomavirus type 16 L1 as a potential live vaccine against cervical cancer and typhoid fever","volume":"14","author":"D Fraillery","year":"2007","journal-title":"Clinical and vaccine immunology: CVI"},{"issue":"201","key":"ref10","first-page":"201","article-title":"Attenuated <italic>Salmonella<\/italic> carrying plasmid HPV18-L1 for prevention of human Papillomavirus (HPV) infection","volume":"29","author":"SH Zhao","year":"2013","journal-title":"Acta Medica Mediterranea"},{"issue":"6","key":"ref11","doi-asserted-by":"crossref","first-page":"1260","DOI":"10.1093\/infdis\/155.6.1260","article-title":"Prevention of shigellosis by a <italic>Salmonella<\/italic> typhi-<italic>Shigella sonnei<\/italic> bivalent vaccine","volume":"155","author":"RE Black","year":"1987","journal-title":"The Journal of infectious diseases"},{"issue":"7\u20138","key":"ref12","doi-asserted-by":"crossref","first-page":"678","DOI":"10.1016\/S0264-410X(02)00579-0","article-title":"Experience with registered mucosal vaccines","volume":"21","author":"G Dietrich","year":"2003","journal-title":"Vaccine"},{"issue":"2","key":"ref13","doi-asserted-by":"crossref","first-page":"97","DOI":"10.1078\/1438-4221-00106","article-title":"Breaking through the acid barrier: an orchestrated response to proton stress by enteric bacteria","volume":"291","author":"JP Audia","year":"2001","journal-title":"International journal of medical microbiology: IJMM"},{"issue":"2","key":"ref14","first-page":"301","article-title":"Acid stress response in enteropathogenic gammaproteobacteria: an aptitude for survival","volume":"88","author":"B Zhao","year":"2010","journal-title":"Biochemistry and cell biology"},{"issue":"4","key":"ref15","doi-asserted-by":"crossref","first-page":"770","DOI":"10.1111\/mmi.12020","article-title":"Glutamate decarboxylase-dependent acid resistance in orally acquired bacteria: function, distribution and biomedical implications of the <italic>gadBC<\/italic> operon","volume":"86","author":"D De Biase","year":"2012","journal-title":"Molecular microbiology"},{"issue":"13","key":"ref16","doi-asserted-by":"crossref","first-page":"3062","DOI":"10.1128\/JB.00104-13","article-title":"Low-pH rescue of acid-sensitive <italic>Salmonella enterica<\/italic> Serovar Typhi Strains by a Rhamnose-regulated arginine decarboxylase system","volume":"195","author":"KE Brenneman","year":"2013","journal-title":"Journal of bacteriology"},{"issue":"9","key":"ref17","doi-asserted-by":"crossref","first-page":"2596","DOI":"10.1128\/jb.176.9.2596-2602.1994","article-title":"Acid-sensitive mutants of <italic>Salmonella<\/italic> typhimurium identified through a dinitrophenol lethal screening strategy","volume":"176","author":"JW Foster","year":"1994","journal-title":"Journal of bacteriology"},{"issue":"2","key":"ref18","doi-asserted-by":"crossref","first-page":"170","DOI":"10.1016\/S1369-5274(99)80030-7","article-title":"When protons attack: microbial strategies of acid adaptation","volume":"2","author":"JW Foster","year":"1999","journal-title":"Current opinion in microbiology"},{"issue":"4","key":"ref19","doi-asserted-by":"crossref","first-page":"215","DOI":"10.3109\/10408419509113541","article-title":"Low pH adaptation and the acid tolerance response of <italic>Salmonella<\/italic> typhimurium","volume":"21","author":"JW Foster","year":"1995","journal-title":"Critical reviews in microbiology"},{"issue":"1","key":"ref20","doi-asserted-by":"crossref","first-page":"141","DOI":"10.1111\/j.1574-6968.1999.tb13366.x","article-title":"The rpoS mutant allele of <italic>Salmonella<\/italic> typhi Ty2 is identical to that of the live typhoid vaccine Ty21a","volume":"170","author":"V Robbe-Saule","year":"1999","journal-title":"FEMS microbiology letters"},{"issue":"4","key":"ref21","article-title":"Genome Sequence of <italic>Salmonella enterica<\/italic> Serovar Typhi Oral Vaccine Strain Ty21a","volume":"1","author":"D Xu","year":"2013","journal-title":"Genome announcements"},{"issue":"10","key":"ref22","doi-asserted-by":"crossref","first-page":"895","DOI":"10.1016\/0264-410X(94)90031-0","article-title":"Adaptive acid tolerance response by <italic>Salmonella<\/italic> typhi and candidate live oral typhoid vaccine strains","volume":"12","author":"DM Hone","year":"1994","journal-title":"Vaccine"},{"issue":"5","key":"ref23","doi-asserted-by":"crossref","first-page":"553","DOI":"10.1093\/infdis\/131.5.553","article-title":"Isolation and characterization of Gal E mutant Ty 21a of <italic>Salmonella<\/italic> typhi: a candidate strain for a live, oral typhoid vaccine","volume":"131","author":"R Germanier","year":"1975","journal-title":"The Journal of infectious diseases"},{"issue":"7","key":"ref24","doi-asserted-by":"crossref","first-page":"e22397","DOI":"10.1371\/journal.pone.0022397","article-title":"Sensing and adaptation to low pH mediated by inducible amino acid decarboxylases in Salmonella","volume":"6","author":"JP Viala","year":"2011","journal-title":"PLOS ONE"},{"issue":"6","key":"ref25","doi-asserted-by":"crossref","first-page":"1096","DOI":"10.1093\/clinids\/4.6.1096","article-title":"A review of human salmonellosis: I. Infective dose","volume":"4","author":"MJ Blaser","year":"1982","journal-title":"Reviews of infectious diseases"},{"key":"ref26","first-page":"361","article-title":"Study of induced typhoid fever in man. I. Evaluation of vaccine effectiveness","volume":"79","author":"RB Hornick","year":"1966","journal-title":"Transactions of the Association of American Physicians"},{"issue":"6","key":"ref27","doi-asserted-by":"crossref","first-page":"1126","DOI":"10.1093\/infdis\/159.6.1126","article-title":"Inoculum size in shigellosis and implications for expected mode of transmission","volume":"159","author":"HL DuPont","year":"1989","journal-title":"The Journal of infectious diseases"},{"issue":"8720","key":"ref28","doi-asserted-by":"crossref","first-page":"891","DOI":"10.1016\/0140-6736(90)92266-K","article-title":"Comparison of enteric-coated capsules and liquid formulation of Ty21a typhoid vaccine in randomised controlled field trial","volume":"336","author":"MM Levine","year":"1990","journal-title":"Lancet"},{"issue":"6","key":"ref29","first-page":"957","article-title":"Vaccination against typhoid fever: present status","volume":"72","author":"B Ivanoff","year":"1994","journal-title":"Bulletin of the World Health Organization"},{"issue":"5","key":"ref30","doi-asserted-by":"crossref","first-page":"1021","DOI":"10.1016\/j.femsre.2005.03.005","article-title":"<italic>Salmonella<\/italic> stress management and its relevance to behaviour during intestinal colonisation and infection","volume":"29","author":"I Rychlik","year":"2005","journal-title":"FEMS microbiology reviews"},{"key":"ref31","first-page":"161","article-title":"Typhoid fever &amp; vaccine development: a partially answered question","volume":"135","author":"SA Marathe","year":"2012","journal-title":"The Indian journal of medical research"},{"issue":"1","key":"ref32","doi-asserted-by":"crossref","first-page":"104","DOI":"10.1016\/j.plasmid.2012.07.005","article-title":"Complete sequence of the suicide vector pJP5603","volume":"69","author":"T Riedel","year":"2013","journal-title":"Plasmid"},{"issue":"20","key":"ref33","doi-asserted-by":"crossref","first-page":"6496","DOI":"10.1128\/AEM.01669-09","article-title":"Versatile dual-technology system for markerless allele replacement in <italic>Burkholderia pseudomallei<\/italic>","volume":"75","author":"CM Lopez","year":"2009","journal-title":"Applied and environmental microbiology"},{"issue":"1","key":"ref34","doi-asserted-by":"crossref","first-page":"9","DOI":"10.1016\/0378-1119(95)00193-A","article-title":"Gene disruption in <italic>Escherichia coli<\/italic>: TcR and KmR cassettes with the option of Flp-catalyzed excision of the antibiotic-resistance determinant","volume":"158","author":"PP Cherepanov","year":"1995","journal-title":"Gene"},{"issue":"1","key":"ref35","doi-asserted-by":"crossref","first-page":"139","DOI":"10.1111\/j.1574-6968.2004.tb09525.x","article-title":"Comparative analysis of transcriptional regulatory elements of glutamate-dependent acid-resistance systems of <italic>Shigella flexneri<\/italic> and <italic>Escherichia coli<\/italic> O157:H7","volume":"234","author":"AA Bhagwat","year":"2004","journal-title":"FEMS microbiology letters"},{"issue":"4","key":"ref36","doi-asserted-by":"crossref","first-page":"353","DOI":"10.1016\/S0092-1157(89)80006-X","article-title":"<italic>Salmonella<\/italic> typhi vaccine strain in vitro; low infectivity in human cell line U937","volume":"17","author":"EM Dragunsky","year":"1989","journal-title":"Journal of biological standardization"},{"issue":"2","key":"ref37","doi-asserted-by":"crossref","first-page":"331","DOI":"10.1111\/j.1365-2958.2008.06276.x","article-title":"A basic\/hydrophobic cleft of the T4 activator MotA interacts with the C-terminus of E.coli sigma70 to activate middle gene transcription","volume":"69","author":"RP Bonocora","year":"2008","journal-title":"Molecular microbiology"},{"issue":"13","key":"ref38","doi-asserted-by":"crossref","first-page":"4120","DOI":"10.1073\/pnas.81.13.4120","article-title":"Regulation of the <italic>araC<\/italic> gene of <italic>Escherichia coli<\/italic>: catabolite repression, autoregulation, and effect on <italic>araBAD<\/italic> expression","volume":"81","author":"CG Miyada","year":"1984","journal-title":"Proceedings of the National Academy of Sciences of the United States of America"},{"issue":"1","key":"ref39","doi-asserted-by":"crossref","first-page":"155","DOI":"10.1016\/S0378-1097(03)00508-1","article-title":"Identification of the promoter regions and sigma(s)-dependent regulation of the <italic>gadA<\/italic> and <italic>gadBC<\/italic> genes associated with glutamate-dependent acid resistance in <italic>Shigella flexneri<\/italic>","volume":"225","author":"SR Waterman","year":"2003","journal-title":"FEMS microbiology letters"},{"issue":"5","key":"ref40","doi-asserted-by":"crossref","first-page":"609","DOI":"10.1111\/j.1365-2958.1989.tb00208.x","article-title":"Construction of lac fusions to the inducible arginine- and lysine decarboxylase genes of <italic>Escherichia coli<\/italic> K12","volume":"3","author":"EA Auger","year":"1989","journal-title":"Molecular microbiology"},{"issue":"46","key":"ref41","doi-asserted-by":"crossref","first-page":"19515","DOI":"10.1073\/pnas.0910586106","article-title":"Cellular stress created by intermediary metabolite imbalances","volume":"106","author":"SJ Lee","year":"2009","journal-title":"Proceedings of the National Academy of Sciences of the United States of America"},{"issue":"3","key":"ref42","doi-asserted-by":"crossref","first-page":"231","DOI":"10.1016\/j.plasmid.2013.02.003","article-title":"Plasmid R6K replication control","volume":"69","author":"SA Rakowski","year":"2013","journal-title":"Plasmid"},{"key":"ref43","doi-asserted-by":"crossref","first-page":"164","DOI":"10.3389\/fmicb.2012.00164","article-title":"<italic>Salmonella enterica<\/italic>: a surprisingly well-adapted intracellular lifestyle","volume":"3","author":"T Dandekar","year":"2012","journal-title":"Frontiers in microbiology"},{"key":"ref44","article-title":"Molecular Cloning: A Laboratory Manual","author":"J Sambrook","year":"1989"},{"issue":"6","key":"ref45","doi-asserted-by":"crossref","first-page":"431","DOI":"10.3855\/jidc.157","article-title":"Typhi genes expressed during infection or involved in pathogenesis","volume":"2","author":"F Daigle","year":"2008","journal-title":"Journal of infection in developing countries"},{"issue":"1","key":"ref46","doi-asserted-by":"crossref","first-page":"55","DOI":"10.1111\/j.1574-695X.1995.tb00175.x","article-title":"<italic>Salmonella<\/italic> typhi does not inhibit phagosome-lysosome fusion in human monocyte-derived macrophages","volume":"12","author":"Y Ishibashi","year":"1995","journal-title":"FEMS immunology and medical microbiology"},{"issue":"5","key":"ref47","doi-asserted-by":"crossref","first-page":"405","DOI":"10.1016\/j.jinf.2014.01.006","article-title":"Advancing the management and control of typhoid fever: a review of the historical role of human challenge studies","volume":"68","author":"CS Waddington","year":"2014","journal-title":"The Journal of infection"},{"key":"ref48","doi-asserted-by":"crossref","first-page":"189","DOI":"10.1146\/annurev-micro-090110-102946","article-title":"The RpoS-mediated general stress response in <italic>Escherichia coli<\/italic>","volume":"65","author":"A Battesti","year":"2011","journal-title":"Annual review of microbiology"},{"issue":"2","key":"ref49","doi-asserted-by":"crossref","first-page":"171","DOI":"10.1111\/j.1574-6968.1995.tb07412.x","article-title":"The live oral typhoid vaccine Ty21a is a rpoS mutant and is susceptible to various environmental stresses","volume":"126","author":"V Robbe-Saule","year":"1995","journal-title":"FEMS microbiology letters"},{"key":"ref50","first-page":"9","article-title":"Immunogenicity of Ty21a attenuated &quot;<italic>Salmonella<\/italic> typhi&quot; given with sodium bicarbonate or in enteric-coated capsules","volume":"53","author":"R Black","year":"1983","journal-title":"Developments in biological standardization"}],"container-title":["PLOS ONE"],"original-title":[],"language":"en","link":[{"URL":"http:\/\/dx.plos.org\/10.1371\/journal.pone.0163511","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2020,5,9]],"date-time":"2020-05-09T10:12:32Z","timestamp":1589019152000},"score":1,"resource":{"primary":{"URL":"https:\/\/dx.plos.org\/10.1371\/journal.pone.0163511"}},"subtitle":[],"editor":[{"given":"Mikael","family":"Skurnik","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"editor"}]}],"short-title":[],"issued":{"date-parts":[[2016,9,27]]},"references-count":50,"journal-issue":{"issue":"9","published-online":{"date-parts":[[2016,9,27]]}},"URL":"https:\/\/doi.org\/10.1371\/journal.pone.0163511","relation":{},"ISSN":["1932-6203"],"issn-type":[{"value":"1932-6203","type":"electronic"}],"subject":[],"published":{"date-parts":[[2016,9,27]]}}}