Designer vaccines to prevent infections due to group B Streptococcus.
Group B streptococci (GBS) are the major cause of serious infections in neonates and an important cause of infection in adults, particularly peripartum women and patients with diabetes mellitus and malignancy. Immunity to GBS in neonates is associated with naturally acquired maternal antibodies to the type-specific capsular polysaccharides of these organisms. IgG class antibodies directed to these polysaccharides are passed transplacentally and protect the child from invasive GBS disease. Phase I and II clinical trials showed that the purified polysaccharides had limited immunogenicity. However, vaccine responders passed functional IgG class antibodies to their children. A glycoconjugate vaccine has been designed so that the type-specific polysaccharides are covalently linked to a carrier protein. This secondary amine linkage is between aldehyde groups created on the eighth carbon of a selected number of periodate-oxidized sialic acid residues of the polysaccharide and epsilon-amino groups on lysine residues of tetanus toxoid. Careful epitope mapping studies had demonstrated that modification by controlled periodate oxidation could be accomplished and that an important conformational epitope on the polysaccharide would be preserved. Preclinical testing of the glycoconjugate vaccines in animal models of GBS disease demonstrated the immunogenicity and protective efficacy of the vaccine-induced antibodies. Phase I clinical testing of the glycoconjugate vaccine is in progress, and the early results appear promising.
Kasper
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DL
Channing Laboratory, Department of Medicine, Brigham and Women's Hospital, Boston, MA 02115, USA.
D001428:Bacterial Vaccines / Q000627:therapeutic use*; D002240:Carbohydrate Sequence; D005260:Female; D006023:Glycoproteins / Q000276:immunology; D006801:Humans; D007231:Infant, Newborn; D008969:Molecular Sequence Data; D011135:Polysaccharides, Bacterial / Q000276:immunology; D013290:Streptococcal Infections / Q000517:prevention & control*; D013292:Streptococcus agalactiae / Q000276:immunology*; D014614:Vaccines, Synthetic / Q000627:therapeutic use*
D001428:Bacterial Vaccines; D006023:Glycoproteins; D011135:Polysaccharides, Bacterial; D014614:Vaccines, Synthetic