title: Synthesis of a conjugate vaccine composed of pneumococcus type 14 capsular polysaccharide bound to pertussis toxin.
abstract: Type 14 is one of the common types isolated from patients of all ages with infections caused by Streptococcus pneumoniae. Its capsular polysaccharide (Pn14) is composed of a neutrally charged tetrasaccharide repeat unit. Pn14 does not elicit protective levels of antibodies in infants and children and is a less than optimal immunogen of the 23-valent vaccine for adults. Pertussis toxin (PT) is both a virulence factor and protective antigen of Bordetella pertussis: it is not soluble at neutral pH and forms insoluble complexes with acidic polysaccharides. Both Pn14 and PT are potential components of vaccines for infants and children. Accordingly, a synthetic scheme was devised to prepare a conjugate of Pn14 and PT. An adipic acid hydrazide derivative of Pn14 was bound to PT at pH 3.9 by carbodiimide-mediated condensation. The conjugation procedure inactivated the PT as assayed by CHO cell and histamine-sensitizing activity. The Pn14-PT conjugate elicited antibodies in mice to Pn14 at levels estimated to be protective in humans and elicited neutralizing antibodies to PT. We plan to evaluate Pn14-PT clinically.
authors.affiliation: Laboratory of Developmental and Molecular Immunity, National Institute of Child Health and Human Development, National Institutes of Health, Bethesda, Maryland 20892.
authors.forename: R
authors.initials: R
authors.lastname: Schneerson
authors.forename: L
authors.initials: L
authors.lastname: Levi
authors.forename: J B
authors.initials: JB
authors.lastname: Robbins
authors.forename: D M
authors.initials: DM
authors.lastname: Bryla
authors.forename: G
authors.initials: G
authors.lastname: Schiffman
authors.forename: T
authors.initials: T
authors.lastname: Lagergard
mesh_terms: D000818:Animals; D000907:Antibodies, Bacterial / Q000032:analysis; D001428:Bacterial Vaccines / Q000276:immunology*; D002240:Carbohydrate Sequence; D005260:Female; D007114:Immunization; D051379:Mice; D008969:Molecular Sequence Data; D037342:Pertussis Toxin; D011135:Polysaccharides, Bacterial / Q000276:immunology*; D013296:Streptococcus pneumoniae / Q000276:immunology*; D014614:Vaccines, Synthetic / Q000276:immunology*; D010566:Virulence Factors, Bordetella / Q000276:immunology*
chemical_list: D000907:Antibodies, Bacterial; D001428:Bacterial Vaccines; D011135:Polysaccharides, Bacterial; D014614:Vaccines, Synthetic; D010566:Virulence Factors, Bordetella; D037342:Pertussis Toxin