title: Acid-detoxified Inaba lipopolysaccharide (pmLPS) is a superior cholera conjugate vaccine immunogen than hydrazine-detoxified lipopolysaccharide and induces vibriocidal and protective antibodies.
abstract: Worldwide, in endemic areas of cholera, the group most burdened with cholera is children. This is especially vexing as young children (2-5 years of age) do not respond as well, or for as long as adults do, to the current killed oral cholera vaccines (OCV). Conjugate vaccines based on the hapten-carrier paradigm have been developed for several bacterial pathogens that cause widespread and severe diseases in young children. We and others have studied different formulations of Vibrio cholerae (Vc) O1 lipopolysaccharide (LPS, a T-independent antigen) conjugates. Detoxified LPS is a central component of a LPS-based conjugate vaccine. pmLPS, which is detoxified by acid treatment, is a superior immunogen compared with hydrazine-detoxified LPS (DetAcLPS) that has altered lipid A acyl chains. The other feature of pmLPS is the ability to link carrier proteins to a core region of sugar. pmLPS readily induced vibriocidal antibodies following one intraperitoneal dose in a MPL-type adjuvant One dose of the pmLPS conjugate was suggestive of being protective; a booster resulted in protective antibodies for infant mice challenged with virulent cholera.
authors.affiliation: LUNAM Université, Unité Fonctionnalité et Ingénierie des Protéines, Nantes, France.
authors.forename: Cyrille
authors.initials: C
authors.lastname: Grandjean
authors.forename: Terri K
authors.initials: TK
authors.lastname: Wade
authors.forename: David
authors.initials: D
authors.lastname: Ropartz
authors.forename: Logan
authors.initials: L
authors.lastname: Ernst
authors.forename: William F
authors.initials: WF
authors.lastname: Wade
mesh_terms: D019342:Acetic Acid / Q000494:pharmacology; D000818:Animals; D000907:Antibodies, Bacterial / Q000097:blood* / Q000276:immunology; D002771:Cholera / Q000276:immunology* / Q000382:microbiology / Q000517:prevention & control*; D022121:Cholera Vaccines / Q000737:chemistry / Q000276:immunology*; D005260:Female; D006801:Humans; D006834:Hydrazines / Q000494:pharmacology; D008070:Lipopolysaccharides / Q000737:chemistry / Q000276:immunology*; D051379:Mice; D018074:Vaccines, Conjugate / Q000737:chemistry / Q000276:immunology*; D014734:Vibrio cholerae / Q000187:drug effects / Q000276:immunology / Q000472:pathogenicity*
chemical_list: D000907:Antibodies, Bacterial; D022121:Cholera Vaccines; D006834:Hydrazines; D008070:Lipopolysaccharides; D018074:Vaccines, Conjugate; C029424:hydrazine; D019342:Acetic Acid