{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,4,30]],"date-time":"2026-04-30T19:24:58Z","timestamp":1777577098126,"version":"3.51.4"},"reference-count":49,"publisher":"American Society for Microbiology","issue":"4","content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Clin. Vaccine Immunol."],"published-print":{"date-parts":[[2012,4]]},"abstract":"<jats:title>ABSTRACT<\/jats:title><jats:p>A shortcoming of currently available oral cholera vaccines is their induction of relatively short-term protection against cholera compared to that afforded by wild-type disease. We were interested in whether transcutaneous or subcutaneous boosting using a neoglycoconjugate vaccine made from a synthetic terminal hexasaccharide of the O-specific polysaccharide of<jats:named-content content-type=\"genus-species\">Vibrio cholerae<\/jats:named-content>O1 (Ogawa) coupled to bovine serum albumin as a carrier (CHO-BSA) could boost lipopolysaccharide (LPS)-specific and vibriocidal antibody responses and result in protective immunity following oral priming immunization with whole-cell cholera vaccine. We found that boosting with CHO-BSA with immunoadjuvantative cholera toxin (CT) or<jats:named-content content-type=\"genus-species\">Escherichia coli<\/jats:named-content>heat-labile toxin (LT) following oral priming with attenuated<jats:named-content content-type=\"genus-species\">V. cholerae<\/jats:named-content>O1 vaccine strain O395-NT resulted in significant increases in serum anti-<jats:named-content content-type=\"genus-species\">V. cholerae<\/jats:named-content>LPS IgG, IgM, and IgA (<jats:italic>P<\/jats:italic>&lt; 0.01) responses as well as in anti-Ogawa (<jats:italic>P<\/jats:italic>&lt; 0.01) and anti-Inaba (<jats:italic>P<\/jats:italic>&lt; 0.05) vibriocidal titers in mice. The LPS-specific IgA responses in stool were induced by transcutaneous (<jats:italic>P<\/jats:italic>&lt; 0.01) but not subcutaneous immunization. Immune responses following use of CT or LT as an adjuvant were comparable. In a neonatal mouse challenge assay, immune serum from boosted mice was associated with 79% protective efficacy against death. Our results suggest that transcutaneous and subcutaneous boosting with a neoglycoconjugate following oral cholera vaccination may be an effective strategy to prolong protective immune responses against<jats:named-content content-type=\"genus-species\">V. cholerae<\/jats:named-content>.<\/jats:p>","DOI":"10.1128\/cvi.05689-11","type":"journal-article","created":{"date-parts":[[2012,2,23]],"date-time":"2012-02-23T01:51:51Z","timestamp":1329961911000},"page":"594-602","source":"Crossref","is-referenced-by-count":20,"title":["Transcutaneous Immunization with a Vibrio cholerae O1 Ogawa Synthetic Hexasaccharide Conjugate following Oral Whole-Cell Cholera Vaccination Boosts Vibriocidal Responses and Induces Protective Immunity in Mice"],"prefix":"10.1128","volume":"19","author":[{"given":"A. A.","family":"Tarique","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"A.","family":"Kalsy","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"M.","family":"Arifuzzaman","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"S. M.","family":"Rollins","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"R. C.","family":"Charles","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"D. T.","family":"Leung","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"J. B.","family":"Harris","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"R. C.","family":"LaRocque","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"A.","family":"Sheikh","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"M. S.","family":"Bhuiyan","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"R.","family":"Saksena","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"J. D.","family":"Clements","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"S. B.","family":"Calderwood","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"F.","family":"Qadri","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"P.","family":"Kov\u00e1\u010d","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"E. T.","family":"Ryan","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"235","published-online":{"date-parts":[[2012,2,22]]},"reference":[{"key":"key20180919073602_B1","doi-asserted-by":"crossref","first-page":"1433","DOI":"10.1016\/j.vaccine.2008.12.036","article-title":"Enhanced immunogenicity of an oral inactivated cholera vaccine in infants in Bangladesh obtained by zinc supplementation and by temporary withholding breast-feeding","volume":"27","author":"Ahmed","year":"2009","journal-title":"Vaccine"},{"key":"key20180919073602_B2","doi-asserted-by":"crossref","first-page":"709","DOI":"10.1093\/infdis\/169.3.709","article-title":"Lack of cross-protection against diarrhea due to Vibrio cholerae O1 after oral immunization of rabbits with V. cholerae O139 Bengal","volume":"169","author":"Albert","year":"1994","journal-title":"J. Infect. Dis."},{"key":"key20180919073602_B3","doi-asserted-by":"crossref","first-page":"912","DOI":"10.1093\/infdis\/jir416","article-title":"Natural cholera infection-derived immunity in an endemic setting","volume":"204","author":"Ali","year":"2011","journal-title":"J. Infect. Dis."},{"key":"key20180919073602_B4","doi-asserted-by":"crossref","first-page":"479","DOI":"10.1016\/S0008-6215(01)00018-0","article-title":"Conjugating oligosaccharides to proteins by squaric acid diester chemistry: rapid monitoring of the progress of conjugation, and recovery of the unused ligand","volume":"330","author":"Chernyak","year":"2001","journal-title":"Carbohydr. Res."},{"key":"key20180919073602_B5","doi-asserted-by":"crossref","first-page":"950","DOI":"10.1086\/339583","article-title":"Induction of protective immunity by synthetic Vibrio cholerae hexasaccharide derived from V. cholerae O1 Ogawa lipopolysaccharide bound to a protein carrier","volume":"185","author":"Chernyak","year":"2002","journal-title":"J. Infect. Dis."},{"key":"key20180919073602_B6","doi-asserted-by":"crossref","first-page":"6391","DOI":"10.1128\/IAI.68.11.6391-6397.2000","article-title":"Construction of a Vibrio cholerae vaccine candidate using transposon delivery and FLP recombinase-mediated excision","volume":"68","author":"Chiang","year":"2000","journal-title":"Infect. Immun."},{"key":"key20180919073602_B7","doi-asserted-by":"crossref","first-page":"2117","DOI":"10.1128\/IAI.01426-09","article-title":"Concomitant enterotoxigenic Escherichia coli infection induces increased immune responses to Vibrio cholerae O1 antigens in patients with cholera in Bangladesh","volume":"78","author":"Chowdhury","year":"2010","journal-title":"Infect. Immun."},{"key":"key20180919073602_B8","doi-asserted-by":"crossref","first-page":"760","DOI":"10.1128\/IAI.24.3.760-769.1979","article-title":"Isolation and characterization of homogeneous heat-labile enterotoxins with high specific activity from Escherichia coli cultures","volume":"24","author":"Clements","year":"1979","journal-title":"Infect. Immun."},{"key":"key20180919073602_B9","doi-asserted-by":"crossref","first-page":"269","DOI":"10.1016\/0264-410X(88)90223-X","article-title":"Adjuvant activity of Escherichia coli heat-labile enterotoxin and effect on the induction of oral tolerance in mice to unrelated protein antigens","volume":"6","author":"Clements","year":"1988","journal-title":"Vaccine"},{"key":"key20180919073602_B10","doi-asserted-by":"crossref","first-page":"977","DOI":"10.1128\/IAI.68.2.977-981.2000","article-title":"Optimizing the germfree mouse model for in vivo evaluation of oral Vibrio cholerae vaccine and vector strains","volume":"68","author":"Crean","year":"2000","journal-title":"Infect. Immun."},{"key":"key20180919073602_B11","doi-asserted-by":"crossref","first-page":"1617","DOI":"10.1128\/IAI.63.5.1617-1623.1995","article-title":"Dissociation of Escherichia coli heat-labile enterotoxin adjuvanticity from ADP-ribosyltransferase activity","volume":"63","author":"Dickinson","year":"1995","journal-title":"Infect. Immun."},{"key":"key20180919073602_B12","doi-asserted-by":"crossref","first-page":"2826","DOI":"10.1128\/IAI.00127-07","article-title":"Transcutaneous immunization with Clostridium difficile toxoid A induces systemic and mucosal immune responses and toxin A-neutralizing antibodies in mice","volume":"75","author":"Ghose","year":"2007","journal-title":"Infect. Immun."},{"key":"key20180919073602_B13","doi-asserted-by":"crossref","first-page":"797","DOI":"10.1517\/13543784.8.6.797","article-title":"Advances in vaccine delivery: transcutaneous immunisation","volume":"8","author":"Glenn","year":"1999","journal-title":"Expert Opin. Investig. Drugs"},{"key":"key20180919073602_B14","doi-asserted-by":"crossref","first-page":"1100","DOI":"10.1128\/IAI.67.3.1100-1106.1999","article-title":"Transcutaneous immunization with bacterial ADP-ribosylating exotoxins as antigens and adjuvants","volume":"67","author":"Glenn","year":"1999","journal-title":"Infect. Immun."},{"key":"key20180919073602_B15","doi-asserted-by":"crossref","first-page":"e221","DOI":"10.1371\/journal.pntd.0000221","article-title":"Susceptibility to Vibrio cholerae infection in a cohort of household contacts of patients with cholera in Bangladesh","volume":"2","author":"Harris","year":"2008","journal-title":"PLoS Negl. Trop. Dis."},{"key":"key20180919073602_B16","doi-asserted-by":"crossref","first-page":"e403","DOI":"10.1371\/journal.pntd.0000403","article-title":"Immunologic responses to Vibrio cholerae in patients co-infected with intestinal parasites in Bangladesh","volume":"3","author":"Harris","year":"2009","journal-title":"PLoS Negl. Trop. Dis."},{"key":"key20180919073602_B17","doi-asserted-by":"crossref","first-page":"2720","DOI":"10.1016\/S0264-410X(02)00208-6","article-title":"Comparison of mucosal and systemic humoral immune responses after transcutaneous and oral immunization strategies","volume":"20","author":"John","year":"2002","journal-title":"Vaccine"},{"key":"key20180919073602_B18","doi-asserted-by":"crossref","first-page":"2108","DOI":"10.1128\/IAI.62.5.2108-2110.1994","article-title":"Vibrio cholerae O139 synonym Bengal is closely related to Vibrio cholerae El Tor but has important differences","volume":"62","author":"Johnson","year":"1994","journal-title":"Infect. Immun."},{"key":"key20180919073602_B19","doi-asserted-by":"crossref","first-page":"877","DOI":"10.1038\/nature07084","article-title":"Inapparent infections and cholera dynamics","volume":"454","author":"King","year":"2008","journal-title":"Nature"},{"key":"key20180919073602_B20","doi-asserted-by":"crossref","first-page":"696","DOI":"10.1038\/nature03820","article-title":"Refractory periods and climate forcing in cholera dynamics","volume":"436","author":"Koelle","year":"2005","journal-title":"Nature"},{"key":"key20180919073602_B21","doi-asserted-by":"crossref","first-page":"34","DOI":"10.1128\/CMR.8.1.34","article-title":"The family of bacterial ADP-ribosylating exotoxins","volume":"8","author":"Krueger","year":"1995","journal-title":"Clin. Microbiol. Rev."},{"key":"key20180919073602_B22","doi-asserted-by":"crossref","first-page":"1709","DOI":"10.1086\/315051","article-title":"Effect of small bowel bacterial overgrowth on the immunogenicity of single-dose live oral cholera vaccine CVD 103-HgR","volume":"180","author":"Lagos","year":"1999","journal-title":"J. Infect. Dis."},{"key":"key20180919073602_B23","doi-asserted-by":"crossref","first-page":"818","DOI":"10.1093\/infdis\/143.6.818","article-title":"Duration of infection-derived immunity to cholera","volume":"143","author":"Levine","year":"1981","journal-title":"J. Infect. Dis."},{"key":"key20180919073602_B24","doi-asserted-by":"crossref","first-page":"10","DOI":"10.1128\/IAI.64.1.10-15.1996","article-title":"Factors influencing secondary vibriocidal immune responses: relevance for understanding immunity to cholera","volume":"64","author":"Losonsky","year":"1996","journal-title":"Infect. Immun."},{"key":"key20180919073602_B25","doi-asserted-by":"crossref","first-page":"3759","DOI":"10.1016\/S0264-410X(01)00088-3","article-title":"Mucosal immunization of mice using CpG DNA and\/or mutants of the heat-labile enterotoxin of Escherichia coli as adjuvants","volume":"19","author":"McCluskie","year":"2001","journal-title":"Vaccine"},{"key":"key20180919073602_B26","doi-asserted-by":"crossref","first-page":"551","DOI":"10.1038\/306551a0","article-title":"Cholera toxin genes: nucleotide sequence, deletion analysis and vaccine development","volume":"306","author":"Mekalanos","year":"1983","journal-title":"Nature"},{"key":"key20180919073602_B27","doi-asserted-by":"crossref","first-page":"505","DOI":"10.1093\/infdis\/121.5.505","article-title":"The antigens of Vibrio cholerae involved in the vibriocidal action of antibody and complement","volume":"121","author":"Neoh","year":"1970","journal-title":"J. Infect. Dis."},{"key":"key20180919073602_B28","doi-asserted-by":"crossref","first-page":"546","DOI":"10.1128\/CVI.00538-10","article-title":"Characterization of a mutant Escherichia coli heat-labile toxin, LT(R192G\/L211A), as a safe and effective oral adjuvant","volume":"18","author":"Norton","year":"2011","journal-title":"Clin. Vaccine Immunol."},{"key":"key20180919073602_B29","doi-asserted-by":"crossref","first-page":"2534","DOI":"10.1016\/S0264-410X(00)00553-3","article-title":"Mucosal vaccines: non toxic derivatives of LT and CT as mucosal adjuvants","volume":"19","author":"Pizza","year":"2001","journal-title":"Vaccine"},{"key":"key20180919073602_B30","doi-asserted-by":"crossref","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":"key20180919073602_B31","doi-asserted-by":"crossref","first-page":"5834","DOI":"10.1128\/IAI.00438-06","article-title":"Transcutaneous immunization with toxin-coregulated pilin A induces protective immunity against Vibrio cholerae O1 El Tor challenge in mice","volume":"74","author":"Rollenhagen","year":"2006","journal-title":"Infect. Immun."},{"key":"key20180919073602_B32","doi-asserted-by":"crossref","first-page":"4917","DOI":"10.1016\/j.vaccine.2009.06.040","article-title":"Transcutaneous immunization with a synthetic hexasaccharide-protein conjugate induces anti-Vibrio cholerae lipopolysaccharide responses in mice","volume":"27","author":"Rollenhagen","year":"2009","journal-title":"Vaccine"},{"key":"key20180919073602_B33","doi-asserted-by":"crossref","first-page":"6270","DOI":"10.1128\/IAI.67.12.6270-6280.1999","article-title":"Mutants of Escherichia coli heat-labile toxin act as effective mucosal adjuvants for nasal delivery of an acellular pertussis vaccine: differential effects of the nontoxic AB complex and enzyme activity on Th1 and Th2 cells","volume":"67","author":"Ryan","year":"1999","journal-title":"Infect. Immun."},{"key":"key20180919073602_B34","doi-asserted-by":"crossref","first-page":"3118","DOI":"10.1128\/IAI.65.8.3118-3125.1997","article-title":"Oral immunization with attenuated vaccine strains of Vibrio cholerae expressing a dodecapeptide repeat of the serine-rich Entamoeba histolytica protein fused to the cholera toxin B subunit induces systemic and mucosal antiamebic and anti-V. cholerae antibody responses in mice","volume":"65","author":"Ryan","year":"1997","journal-title":"Infect. Immun."},{"key":"key20180919073602_B35","doi-asserted-by":"crossref","first-page":"483","DOI":"10.1586\/14760584.5.4.483","article-title":"Live attenuated oral cholera vaccines","volume":"5","author":"Ryan","year":"2006","journal-title":"Expert Rev. Vaccines"},{"key":"key20180919073602_B36","doi-asserted-by":"crossref","first-page":"1694","DOI":"10.1128\/IAI.67.4.1694-1701.1999","article-title":"In vivo expression and immunoadjuvancy of a mutant of heat-labile enterotoxin of Escherichia coli in vaccine and vector strains of Vibrio cholerae.","volume":"67","author":"Ryan","year":"1999","journal-title":"Infect. Immun."},{"key":"key20180919073602_B37","doi-asserted-by":"crossref","first-page":"2256","DOI":"10.1016\/j.carres.2005.07.017","article-title":"Effect of saccharide length on the immunogenicity of neoglycoconjugates from synthetic fragments of the O-SP of Vibrio cholerae O1, serotype Ogawa","volume":"340","author":"Saksena","year":"2005","journal-title":"Carbohydr. Res."},{"key":"key20180919073602_B38","doi-asserted-by":"crossref","first-page":"1343","DOI":"10.1093\/cid\/cir141","article-title":"Oral vaccines against cholera","volume":"52","author":"Shin","year":"2011","journal-title":"Clin. Infect. Dis."},{"key":"key20180919073602_B39","first-page":"CD008603","article-title":"Oral vaccines for preventing cholera","volume":"3","author":"Sinclair","year":"2011","journal-title":"Cochrane Database Syst. Rev."},{"key":"key20180919073602_B40","doi-asserted-by":"crossref","first-page":"317","DOI":"10.1615\/CritRevImmunol.v15.i3-4.70","article-title":"The mucosal adjuvant activities of ADP-ribosylating bacterial enterotoxins","volume":"15","author":"Snider","year":"1995","journal-title":"Crit. Rev. Immunol."},{"key":"key20180919073602_B41","doi-asserted-by":"crossref","first-page":"e1289","DOI":"10.1371\/journal.pntd.0001289","article-title":"Efficacy of a low-cost, inactivated whole-cell oral cholera vaccine: results from 3 years of follow-up of a randomized, controlled trial","volume":"5","author":"Sur","year":"2011","journal-title":"PLoS Negl. Trop. Dis."},{"key":"key20180919073602_B42","doi-asserted-by":"crossref","first-page":"2833","DOI":"10.1073\/pnas.84.9.2833","article-title":"Use of phoA gene fusions to identify a pilus colonization factor coordinately regulated with cholera toxin","volume":"84","author":"Taylor","year":"1987","journal-title":"Proc. Natl. Acad. Sci. U. S. A."},{"key":"key20180919073602_B43","first-page":"6","article-title":"Cadherins and Langerhans cell immunobiology","volume":"107","author":"Udey","year":"1997","journal-title":"Clin. Exp. Immunol."},{"key":"key20180919073602_B44","doi-asserted-by":"crossref","first-page":"237","DOI":"10.1111\/j.1574-695X.2006.00143.x","article-title":"Immunogenicity of synthetic saccharide fragments of Vibrio cholerae O1 (Ogawa and Inaba) bound to Exotoxin A","volume":"48","author":"Wade","year":"2006","journal-title":"FEMS Immunol. Med. Microbiol."},{"key":"key20180919073602_B45","doi-asserted-by":"crossref","first-page":"2777","DOI":"10.1074\/jbc.273.5.2777","article-title":"On the antigenic determinants of the lipopolysaccharides of Vibrio cholerae O:1, serotypes Ogawa and Inaba","volume":"273","author":"Wang","year":"1998","journal-title":"J. Biol. Chem."},{"key":"key20180919073602_B46","first-page":"117","article-title":"Cholera vaccines: WHO position paper","volume":"85","author":"World Health Organization","year":"2010","journal-title":"Wkly. Epidemiol. Rec."},{"key":"key20180919073602_B47","first-page":"309","article-title":"Cholera: global surveillance summary, 2008","volume":"84","author":"World Health Organization","year":"2009","journal-title":"Wkly. Epidemiol. Rec."},{"key":"key20180919073602_B48","doi-asserted-by":"crossref","first-page":"157","DOI":"10.1016\/S0008-6215(99)00185-8","article-title":"Studies on vaccines against cholera. Synthesis of neoglycoconjugates from the hexasaccharide determinant of Vibrio cholerae O:1, serotype Ogawa, by single-point attachment or by attachment of the hapten in the form of clusters","volume":"321","author":"Zhang","year":"1999","journal-title":"Carbohydr. Res."},{"key":"key20180919073602_B49","doi-asserted-by":"crossref","first-page":"521","DOI":"10.1016\/S1473-3099(07)70138-X","article-title":"The true burden and risk of cholera: implications for prevention and control","volume":"7","author":"Zuckerman","year":"2007","journal-title":"Lancet Infect. Dis."}],"container-title":["Clinical and Vaccine Immunology"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/syndication.highwire.org\/content\/doi\/10.1128\/CVI.05689-11","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2021,7,29]],"date-time":"2021-07-29T20:46:49Z","timestamp":1627591609000},"score":1,"resource":{"primary":{"URL":"https:\/\/journals.asm.org\/doi\/10.1128\/CVI.05689-11"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2012,2,22]]},"references-count":49,"journal-issue":{"issue":"4","published-online":{"date-parts":[[2012,3,28]]},"published-print":{"date-parts":[[2012,4]]}},"alternative-id":["10.1128\/CVI.05689-11"],"URL":"https:\/\/doi.org\/10.1128\/cvi.05689-11","relation":{},"ISSN":["1556-6811","1556-679X"],"issn-type":[{"value":"1556-6811","type":"print"},{"value":"1556-679X","type":"electronic"}],"subject":[],"published":{"date-parts":[[2012,2,22]]}}}