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.
abstract: 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 Vibrio cholerae 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 Escherichia coli heat-labile toxin (LT) following oral priming with attenuated V. cholerae O1 vaccine strain O395-NT resulted in significant increases in serum anti-V. cholerae LPS IgG, IgM, and IgA (P < 0.01) responses as well as in anti-Ogawa (P < 0.01) and anti-Inaba (P < 0.05) vibriocidal titers in mice. The LPS-specific IgA responses in stool were induced by transcutaneous (P < 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 V. cholerae.
authors.affiliation: Division of Infectious Diseases, Massachusetts General Hospital, Boston, Massachusetts, USA.
authors.forename: A A
authors.initials: AA
authors.lastname: Tarique
authors.forename: A
authors.initials: A
authors.lastname: Kalsy
authors.forename: M
authors.initials: M
authors.lastname: Arifuzzaman
authors.forename: S M
authors.initials: SM
authors.lastname: Rollins
authors.forename: R C
authors.initials: RC
authors.lastname: Charles
authors.forename: D T
authors.initials: DT
authors.lastname: Leung
authors.forename: J B
authors.initials: JB
authors.lastname: Harris
authors.forename: R C
authors.initials: RC
authors.lastname: Larocque
authors.forename: A
authors.initials: A
authors.lastname: Sheikh
authors.forename: M S
authors.initials: MS
authors.lastname: Bhuiyan
authors.forename: R
authors.initials: R
authors.lastname: Saksena
authors.forename: J D
authors.initials: JD
authors.lastname: Clements
authors.forename: S B
authors.initials: SB
authors.lastname: Calderwood
authors.forename: F
authors.initials: F
authors.lastname: Qadri
authors.forename: P
authors.initials: P
authors.lastname: Kovác
authors.forename: E T
authors.initials: ET
authors.lastname: Ryan
mesh_terms: D000276:Adjuvants, Immunologic / Q000008:administration & dosage; D000279:Administration, Cutaneous; D000284:Administration, Oral; D000818:Animals; D000907:Antibodies, Bacterial / Q000097:blood; D000942:Antigens, Bacterial / Q000008:administration & dosage / Q000276:immunology*; D001427:Bacterial Toxins / Q000008:administration & dosage; D001770:Blood Bactericidal Activity; D002771:Cholera / Q000276:immunology / Q000517:prevention & control*; D002772:Cholera Toxin / Q000008:administration & dosage; D022121:Cholera Vaccines / Q000008:administration & dosage / Q000276:immunology*; D004195:Disease Models, Animal; D004768:Enterotoxins / Q000008:administration & dosage; D029968:Escherichia coli Proteins / Q000008:administration & dosage; D005243:Feces / Q000737:chemistry; D005260:Female; D007117:Immunization, Secondary / Q000379:methods; D007070:Immunoglobulin A / Q000032:analysis / Q000097:blood; D007074:Immunoglobulin G / Q000097:blood; D007075:Immunoglobulin M / Q000097:blood; D007279:Injections, Subcutaneous; D051379:Mice; D009844:Oligosaccharides / Q000008:administration & dosage / Q000276:immunology*; D016019:Survival Analysis; D014613:Vaccines, Attenuated / Q000008:administration & dosage / Q000276:immunology; D018074:Vaccines, Conjugate / Q000008:administration & dosage / Q000276:immunology; D041241:Vibrio cholerae O1 / Q000276:immunology*
chemical_list: D000276:Adjuvants, Immunologic; D000907:Antibodies, Bacterial; D000942:Antigens, Bacterial; D001427:Bacterial Toxins; D022121:Cholera Vaccines; D004768:Enterotoxins; D029968:Escherichia coli Proteins; D007070:Immunoglobulin A; D007074:Immunoglobulin G; D007075:Immunoglobulin M; D009844:Oligosaccharides; D014613:Vaccines, Attenuated; D018074:Vaccines, Conjugate; D002772:Cholera Toxin; C027538:heat-labile enterotoxin, E coli