Group B streptococcal type II and III conjugate vaccines: physicochemical properties that influence immunogenicity.
Recent efforts toward developing vaccines against group B streptococci (GBS) have focused on increasing the immunogenicity of GBS polysaccharides by conjugation to carrier proteins. However, partial depolymerization of GBS polysaccharides for the production of vaccines is a difficult task because of their acid-labile, antigenically critical sialic acids. Here we report a method for the partial depolymerization of type II and III polysaccharides by mild deaminative cleavage to antigenic fragments with reducing-terminal 2,5-anhydro-d-mannose residues. Through the free aldehydes of their newly formed end groups, the fragments were conjugated to tetanus toxoid by reductive amination. The resulting conjugates stimulated the production in animals of high-titer type II- and III-specific antibodies which induced opsonophagocytic killing of type II and III strains of group B streptococci. For the type II conjugates, immunogenicity increased as oligosaccharide size decreased, whereas for type III conjugates, the size of the oligosaccharides did not significantly influence immunogenicity. When oligosaccharides of defined size were conjugated through sialic acid residues, the resulting cross-linkages were shown to affect immunogenicity. When oligosaccharides were conjugated through terminal aldehyde groups generated by deamination, modification of the exocyclic chain of sialic acid did not influence immunogenicity.
Michon
Francis
F
Department of Vaccine Research, BioVeris Corporation, Gaithersburg, MD 20877, USA.
Uitz
Catherine
C
Sarkar
Arun
A
D'Ambra
Anello J
AJ
Laude-Sharp
Maryline
M
Moore
Samuel
S
Fusco
Peter C
PC
D000586:Amination; D000818:Animals; D016667:Bacterial Capsules; D002240:Carbohydrate Sequence; D003429:Cross Reactions; D003641:Deamination; D005260:Female; D007125:Immunogenetics; D009682:Magnetic Resonance Spectroscopy; D051379:Mice; D008969:Molecular Sequence Data; D008970:Molecular Weight; D019158:N-Acetylneuraminic Acid / Q000737:chemistry / Q000276:immunology; D010084:Oxidation-Reduction; D011135:Polysaccharides, Bacterial / Q000737:chemistry* / Q000276:immunology*; D013290:Streptococcal Infections / Q000276:immunology / Q000517:prevention & control; D013292:Streptococcus agalactiae / Q000276:immunology; D013745:Tetanus Toxoid / Q000737:chemistry / Q000276:immunology; D018074:Vaccines, Conjugate / Q000008:administration & dosage / Q000737:chemistry* / Q000276:immunology*
D011135:Polysaccharides, Bacterial; D013745:Tetanus Toxoid; D018074:Vaccines, Conjugate; C038687:capsular polysaccharide, streptococcal group B type II; C032263:streptococcal polysaccharide type III group B; D019158:N-Acetylneuraminic Acid