title: Induction of protective immunity by synthetic Vibrio cholerae hexasaccharide derived from V. cholerae O1 Ogawa lipopolysaccharide bound to a protein carrier.
abstract: Synthetic antigens that mimic the terminal hexasaccharide epitope of the O-specific polysaccharide of Vibrio cholerae O1, serotype Ogawa, were conjugated to bovine serum albumin (BSA). Conjugates with carbohydrate-to-carrier molar ratios of 15.5:1, 9.2:1, and 4.6:1 were tested for immunogenicity and efficacy in mice. The role of preimmunity to BSA and the use of adjuvant in the generation of the serologic response to the O-specific polysaccharide and protection against virulent V. cholerae was examined. Preimmunity to BSA did not affect the anti-Ogawa titers but seemed to enhance the protective capacity of antiserum. All 3 conjugates were immunogenic, but adjuvant was effective at inducing higher and earlier antibody responses. In tertiary serum samples, a correlation was found between vibriocidal activity and protection. The protective capacity of antiserum was evident in serum from mice immunized with all conjugates, but it was highest in the groups that received the conjugate with the lowest level of substitution. Further studies are required to increase understanding of the reason for differential protection.
authors.affiliation: Laboratory of Medicinal Chemistry, National Institute of Diabetes and Digestive and Kidney Diseases, National Institutes of Health, Bethesda, Maryland, USA.
authors.forename: Anatoly
authors.initials: A
authors.lastname: Chernyak
authors.forename: Seiichi
authors.initials: S
authors.lastname: Kondo
authors.forename: Terri K
authors.initials: TK
authors.lastname: Wade
authors.forename: Michael D
authors.initials: MD
authors.lastname: Meeks
authors.forename: Pedro M
authors.initials: PM
authors.lastname: Alzari
authors.forename: Jean-Michel
authors.initials: JM
authors.lastname: Fournier
authors.forename: Ronald K
authors.initials: RK
authors.lastname: Taylor
authors.forename: Pavol
authors.initials: P
authors.lastname: Kovác
authors.forename: William F
authors.initials: WF
authors.lastname: Wade
mesh_terms: D000595:Amino Acid Sequence; D000818:Animals; D000914:Antibodies, Viral / Q000097:blood*; D002771:Cholera / Q000517:prevention & control; D022121:Cholera Vaccines / Q000276:immunology*; D018984:Epitopes, T-Lymphocyte / Q000276:immunology; D005260:Female; D051379:Mice; D008958:Models, Molecular; D008969:Molecular Sequence Data; D019081:O Antigens / Q000737:chemistry / Q000235:genetics / Q000276:immunology*; D012710:Serum Albumin, Bovine / Q000737:chemistry / Q000276:immunology*; D013601:T-Lymphocytes / Q000276:immunology; D014611:Vaccination; D018074:Vaccines, Conjugate / Q000276:immunology; D014734:Vibrio cholerae / Q000276:immunology* / Q000472:pathogenicity
chemical_list: D000914:Antibodies, Viral; D022121:Cholera Vaccines; D018984:Epitopes, T-Lymphocyte; D019081:O Antigens; D018074:Vaccines, Conjugate; D012710:Serum Albumin, Bovine