{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,1,8]],"date-time":"2026-01-08T09:06:01Z","timestamp":1767863161899,"version":"3.49.0"},"reference-count":39,"publisher":"American Society for Microbiology","issue":"1","content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Clin. Vaccine Immunol."],"published-print":{"date-parts":[[2014,1]]},"abstract":"<jats:title>ABSTRACT<\/jats:title><jats:p>Currently, no cholera vaccine is available for persons traveling from the United States to areas of high cholera transmission and who for reasons of occupation or host factors are at increased risk for development of the disease. A single-dose oral cholera vaccine with a rapid onset of protection would be particularly useful for such travelers and might also be an adjunct control measure for cholera outbreaks. The attenuated<jats:named-content content-type=\"genus-species\">Vibrio cholerae<\/jats:named-content>O1 vaccine strain CVD 103-HgR harbors a 94% deletion of the cholera toxin A subunit gene (<jats:italic>ctxA<\/jats:italic>) and has a mercury resistance gene inserted in the gene encoding hemolysin A. We undertook a phase I randomized placebo-controlled two-site trial to assess the safety and immunogenicity of a preliminary formulation of CVD 103-HgR prepared from new master and working cell banks. Healthy young adults were randomized (5:1 vaccinees to placebo recipients) to receive a single oral dose of \u223c4.4 \u00d7 10<jats:sup>8<\/jats:sup>CFU of vaccine or a placebo. Blood serum vibriocidal and cholera toxin-specific IgG antibodies were measured before and 10, 14, and 28 days following vaccination or placebo. Excretion of the vaccine strain in the stool was assessed during the first week postvaccination. A total of 66 subjects were enrolled, comprising 55 vaccinees and 11 placebo recipients. The vaccine was well tolerated. The overall vibriocidal and anti-cholera toxin seroconversion rates were 89% and 57%, respectively. CVD 103-HgR is undergoing renewed manufacture for licensure in the United States under the auspices of PaxVax. Our data mimic those from previous commercial formulations that elicited vibriocidal antibody seroconversion (a correlate of protection) in \u223c90% of vaccinees. (This study has been registered at ClinicalTrials.gov under registration no. NCT01585181.)<\/jats:p>","DOI":"10.1128\/cvi.00601-13","type":"journal-article","created":{"date-parts":[[2013,10,31]],"date-time":"2013-10-31T00:43:57Z","timestamp":1383180237000},"page":"66-73","source":"Crossref","is-referenced-by-count":41,"title":["Safety and Immunogenicity of Single-Dose Live Oral Cholera Vaccine Strain CVD 103-HgR, Prepared from New Master and Working Cell Banks"],"prefix":"10.1128","volume":"21","author":[{"given":"Wilbur H.","family":"Chen","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Richard N.","family":"Greenberg","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Marcela F.","family":"Pasetti","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Sofie","family":"Livio","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Michael","family":"Lock","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Marc","family":"Gurwith","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Myron M.","family":"Levine","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"235","published-online":{"date-parts":[[2013,10,30]]},"reference":[{"key":"key20180919073719_B1","doi-asserted-by":"publisher","DOI":"10.1007\/82_2013_331","article-title":"The cholera outbreak in Haiti: where and how did it begin?","author":"Lantagne","year":"2013","journal-title":"Curr. Top. Microbiol. Immunol."},{"key":"key20180919073719_B2","doi-asserted-by":"publisher","first-page":"80","DOI":"10.1016\/S1477-8939(03)00062-0","article-title":"Cholera: assessing the risk to travellers and identifying methods of protection","volume":"1","author":"Steffen","year":"2003","journal-title":"Travel Med. Infect. Dis."},{"key":"key20180919073719_B3","doi-asserted-by":"publisher","first-page":"2166","DOI":"10.3201\/eid1711.110808","article-title":"Cholera in United States associated with epidemic in Hispaniola","volume":"17","author":"Newton","year":"2011","journal-title":"Emerg. Infect. Dis."},{"key":"key20180919073719_B4","doi-asserted-by":"publisher","first-page":"472","DOI":"10.1097\/QCO.0b013e32834a88af","article-title":"Cholera in the 21st century","volume":"24","author":"Charles","year":"2011","journal-title":"Curr. Opin. Infect. Dis."},{"key":"key20180919073719_B5","doi-asserted-by":"publisher","first-page":"243","DOI":"10.1016\/0020-2452(96)85758-7","article-title":"Live oral cholera vaccine: from principle to product","volume":"93","author":"Levine","year":"1995","journal-title":"B. I. Pasteur"},{"key":"key20180919073719_B6","doi-asserted-by":"publisher","first-page":"2444","DOI":"10.1016\/j.vaccine.2003.11.070","article-title":"Can. oral cholera vaccination play a role in controlling a cholera outbreak?","volume":"22","author":"Calain","year":"2004","journal-title":"Vaccine"},{"key":"key20180919073719_B7","doi-asserted-by":"crossref","first-page":"467","DOI":"10.1016\/S0140-6736(88)90120-1","article-title":"Safety, immunogenicity, and efficacy of recombinant live oral cholera vaccines, CVD 103 and CVD 103-HgR","volume":"2","author":"Levine","year":"1988","journal-title":"Lancet"},{"key":"key20180919073719_B8","doi-asserted-by":"publisher","first-page":"15","DOI":"10.1111\/j.1574-6968.1993.tb06355.x","article-title":"Construction of genetically marked Vibrio cholerae O1 vaccine strains","volume":"111","author":"Ketley","year":"1993","journal-title":"FEMS Microbiol. Lett."},{"key":"key20180919073719_B9","doi-asserted-by":"publisher","first-page":"901","DOI":"10.1016\/0923-2508(90)90128-D","article-title":"Recombinant attenuated Vibrio cholerae strains used as live oral vaccines","volume":"141","author":"Kaper","year":"1990","journal-title":"Res. Microbiol."},{"key":"key20180919073719_B10","first-page":"777","article-title":"The relationship of vibriocidal antibody titre to susceptibility to cholera in family contacts of cholera patients","volume":"38","author":"Mosley","year":"1968","journal-title":"Bull. World Health Organ."},{"key":"key20180919073719_B11","first-page":"335","article-title":"A serological survey for cholera antibodies in rural east Pakistan. 2. A comparison of antibody titres in the innunized [sic] and control populationd [sic] of a cholera-vaccine field-trial area and the relation of antibody titre to cholera case rate","volume":"38","author":"Mosley","year":"1968","journal-title":"Bull. World Health Organ."},{"key":"key20180919073719_B12","doi-asserted-by":"publisher","first-page":"236","DOI":"10.1093\/infdis\/151.2.236","article-title":"Seroepidemiological studies of El Tor cholera in Bangladesh: association of serum antibody levels with protection","volume":"151","author":"Glass","year":"1985","journal-title":"J. Infect. Dis."},{"key":"key20180919073719_B13","doi-asserted-by":"crossref","first-page":"161","DOI":"10.1128\/IAI.56.1.161-167.1988","article-title":"Volunteer studies of deletion mutants of Vibrio cholerae O1 prepared by recombinant techniques","volume":"56","author":"Levine","year":"1988","journal-title":"Infect. Immun."},{"key":"key20180919073719_B14","doi-asserted-by":"crossref","first-page":"6341","DOI":"10.1128\/IAI.67.12.6341-6345.1999","article-title":"Randomized, double-blind, placebo-controlled, multicentered trial of the efficacy of a single dose of live oral cholera vaccine CVD 103-HgR in preventing cholera following challenge with Vibrio cholerae O1 El tor inaba three months after vaccination","volume":"67","author":"Tacket","year":"1999","journal-title":"Infect. Immun."},{"key":"key20180919073719_B15","doi-asserted-by":"crossref","first-page":"2107","DOI":"10.1128\/IAI.65.6.2107-2111.1997","article-title":"Comparison of alternative buffers for use with a new live oral cholera vaccine, Peru-15, in outpatient volunteers","volume":"65","author":"Sack","year":"1997","journal-title":"Infect. Immun."},{"key":"key20180919073719_B16","doi-asserted-by":"publisher","first-page":"407","DOI":"10.1093\/infdis\/164.2.407","article-title":"Antibody responses after immunization with killed oral cholera vaccines during the 1985 vaccine field trial in Bangladesh","volume":"164","author":"Sack","year":"1991","journal-title":"J. Infect. Dis."},{"key":"key20180919073719_B17","doi-asserted-by":"publisher","first-page":"8285","DOI":"10.1016\/j.vaccine.2011.08.108","article-title":"Safety and immunogenicity study of a killed bivalent (O1 and O139) whole-cell oral cholera vaccine Shanchol, in Bangladeshi adults and children as young as 1 year of age","volume":"29","author":"Saha","year":"2011","journal-title":"Vaccine"},{"key":"key20180919073719_B18","doi-asserted-by":"crossref","first-page":"4430","DOI":"10.1128\/IAI.60.10.4430-4432.1992","article-title":"Safety and immunogenicity in North Americans of a single dose of live oral cholera vaccine CVD 103-HgR: results of a randomized, placebo-controlled, double-blind crossover trial","volume":"60","author":"Kotloff","year":"1992","journal-title":"Infect. Immun."},{"key":"key20180919073719_B19","doi-asserted-by":"publisher","first-page":"1042","DOI":"10.1093\/infdis\/165.6.1042","article-title":"Safety and immunogenicity of different immunization regimens of CVD 103-HgR live oral cholera vaccine in soldiers and civilians in Thailand","volume":"165","author":"Su-Arehawaratana","year":"1992","journal-title":"J. Infect. Dis."},{"key":"key20180919073719_B20","doi-asserted-by":"crossref","first-page":"3994","DOI":"10.1128\/IAI.61.9.3994-3997.1993","article-title":"Safety, immunogenicity, and excretion pattern of single-dose live oral cholera vaccine CVD 103-HgR in Peruvian adults of high and low socioeconomic levels","volume":"61","author":"Gotuzzo","year":"1993","journal-title":"Infect. Immun."},{"key":"key20180919073719_B21","doi-asserted-by":"publisher","first-page":"689","DOI":"10.1016\/0140-6736(92)92231-4","article-title":"Safety and immunogenicity of single-dose live oral cholera vaccine CVD 103-HgR in 5-9-year-old Indonesian children","volume":"340","author":"Suharyono","year":"1992","journal-title":"Lancet"},{"key":"key20180919073719_B22","doi-asserted-by":"crossref","first-page":"707","DOI":"10.1128\/IAI.63.2.707-709.1995","article-title":"Attenuated live cholera vaccine strain CVD 103-Hgr elicits significantly higher serum vibriocidal antibody titers in persons of blood group O","volume":"63","author":"Lagos","year":"1995","journal-title":"Infect. Immun."},{"key":"key20180919073719_B23","doi-asserted-by":"publisher","first-page":"1169","DOI":"10.1093\/infdis\/168.5.1169","article-title":"Safety, immunogenicity, and transmissibility of single-dose live oral cholera vaccine strain CVD 103-HgR in 24- to 59-month-old Indonesian children","volume":"168","author":"Simanjuntak","year":"1993","journal-title":"J. Infect. Dis."},{"key":"key20180919073719_B24","doi-asserted-by":"publisher","first-page":"624","DOI":"10.1097\/00006454-199907000-00011","article-title":"Palatability, reactogenicity and immunogenicity of engineered live oral cholera vaccine CVD 103-HgR in Chilean infants and toddlers","volume":"18","author":"Lagos","year":"1999","journal-title":"Pediatr. Infect. Dis. J."},{"key":"key20180919073719_B25","first-page":"63","article-title":"A single dose of live oral cholera vaccine CVD 103-HgR is safe and immunogenic in HIV-infected and HIV-noninfected adults in Mali","volume":"76","author":"Perry","year":"1998","journal-title":"Bull. World Health Organ."},{"key":"key20180919073719_B26","doi-asserted-by":"publisher","first-page":"837","DOI":"10.1093\/infdis\/166.4.837","article-title":"Onset and duration of protective immunity in challenged volunteers after vaccination with live oral cholera vaccine CVD 103-HgR","volume":"166","author":"Tacket","year":"1992","journal-title":"J. Infect. Dis."},{"key":"key20180919073719_B27","doi-asserted-by":"publisher","first-page":"207","DOI":"10.1016\/0264-410X(93)90019-T","article-title":"Live oral vaccines against cholera: an update","volume":"11","author":"Levine","year":"1993","journal-title":"Vaccine"},{"key":"key20180919073719_B28","doi-asserted-by":"publisher","first-page":"1965","DOI":"10.1128\/IAI.70.4.1965-1970.2002","article-title":"Randomized, controlled human challenge study of the safety, immunogenicity, and protective efficacy of a single dose of Peru-15, a live attenuated oral cholera vaccine","volume":"70","author":"Cohen","year":"2002","journal-title":"Infect. Immun."},{"key":"key20180919073719_B29","doi-asserted-by":"publisher","first-page":"328","DOI":"10.1093\/infdis\/142.3.328","article-title":"Selective vs. nonselective media and direct plating vs. enrichment technique in isolation of Vibrio cholerae: recommendations for clinical laboratories","volume":"142","author":"Rennels","year":"1980","journal-title":"J. Infect. Dis."},{"key":"key20180919073719_B30","first-page":"277","article-title":"Serological studies in cholera. 2. The vibriocidal antibody response of cholera patients determined by a microtechnique","volume":"38","author":"Benenson","year":"1968","journal-title":"Bull. World Health Organ."},{"key":"key20180919073719_B31","doi-asserted-by":"crossref","first-page":"174","DOI":"10.1128\/JCM.21.2.174-179.1985","article-title":"Enzyme-linked immunosorbent assay to measure antibodies to purified heat-labile enterotoxins from human and porcine strains of Escherichia coli and to cholera toxin: application in serodiagnosis and seroepidemiology","volume":"21","author":"Levine","year":"1985","journal-title":"J. Clin. Microbiol."},{"key":"key20180919073719_B32","doi-asserted-by":"publisher","first-page":"800","DOI":"10.1093\/biomet\/75.4.800","article-title":"A sharper Bonferroni procedure for multiple tests of significance","volume":"75","author":"Hochberg","year":"1988","journal-title":"Biometrika"},{"key":"key20180919073719_B33","doi-asserted-by":"publisher","first-page":"182","DOI":"10.1093\/infdis\/143.2.182","article-title":"Serologic studies of naturally acquired infection with Vibrio cholerae serogroup O1 in the United States","volume":"143","author":"Snyder","year":"1981","journal-title":"J. Infect. Dis."},{"key":"key20180919073719_B34","doi-asserted-by":"publisher","first-page":"305","DOI":"10.1056\/NEJM198002073020601","article-title":"Cholera\u2013a possible endemic focus in the United States","volume":"302","author":"Blake","year":"1980","journal-title":"N. Engl. J. Med."},{"key":"key20180919073719_B35","doi-asserted-by":"publisher","first-page":"129","DOI":"10.1186\/1741-7007-8-129","article-title":"Immunogenicity and efficacy of oral vaccines in developing countries: lessons from a live cholera vaccine","volume":"8","author":"Levine","year":"2010","journal-title":"BMC Biol."},{"key":"key20180919073719_B36","doi-asserted-by":"publisher","first-page":"2399","DOI":"10.1016\/S0264-410X(00)00006-2","article-title":"Efficacy trial of single-dose live oral cholera vaccine CVD 103-HgR in North Jakarta, Indonesia, a cholera-endemic area","volume":"18","author":"Richie","year":"2000","journal-title":"Vaccine"},{"key":"key20180919073719_B37","doi-asserted-by":"publisher","first-page":"44","DOI":"10.1016\/S0140-6736(05)66550-6","article-title":"Herd immunity conferred by killed oral cholera vaccines in Bangladesh: a reanalysis","volume":"366","author":"Ali","year":"2005","journal-title":"Lancet"},{"key":"key20180919073719_B38","doi-asserted-by":"publisher","first-page":"60","DOI":"10.1093\/infdis\/158.1.60","article-title":"Field trial of oral cholera vaccines in Bangladesh: results of one year of follow-up","volume":"158","author":"Clemens","year":"1988","journal-title":"J. Infect. Dis."},{"key":"key20180919073719_B39","doi-asserted-by":"publisher","first-page":"e336","DOI":"10.1371\/journal.pmed.0040336","article-title":"Controlling endemic cholera with oral vaccines","volume":"4","author":"Longini","year":"2007","journal-title":"PLoS Med."}],"container-title":["Clinical and Vaccine Immunology"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/syndication.highwire.org\/content\/doi\/10.1128\/CVI.00601-13","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2021,7,29]],"date-time":"2021-07-29T20:50:05Z","timestamp":1627591805000},"score":1,"resource":{"primary":{"URL":"https:\/\/journals.asm.org\/doi\/10.1128\/CVI.00601-13"}},"subtitle":[],"editor":[{"given":"D. L.","family":"Burns","sequence":"additional","affiliation":[],"role":[{"role":"editor","vocabulary":"crossref"}]}],"short-title":[],"issued":{"date-parts":[[2013,10,30]]},"references-count":39,"journal-issue":{"issue":"1","published-online":{"date-parts":[[2013,12,31]]},"published-print":{"date-parts":[[2014,1]]}},"alternative-id":["10.1128\/CVI.00601-13"],"URL":"https:\/\/doi.org\/10.1128\/cvi.00601-13","relation":{},"ISSN":["1556-6811","1556-679X"],"issn-type":[{"value":"1556-6811","type":"print"},{"value":"1556-679X","type":"electronic"}],"subject":[],"published":{"date-parts":[[2013,10,30]]}}}