The age-related, T-independent and poor immunologic properties of polysaccharides limit the effectiveness of capsular polysaccharides (CP) and other surface polysaccharides of invasive bacteria as vaccines, in infants and adult individuals with immunocompromised states. Organic synthetic schemes, that bind capsular and other polysaccharides to carrier proteins have been devised to increase the immunogenicity of and confer T-cell dependent immunologic properties (booster effect) to these protective antigens. Based upon our and others work, a conjugated Haemophilus influenzae type b (Hib) vaccine, has been licensed by the Food and Drug Administration for routine infant immunization along with DTP. Serum antibodies to Hib conjugates and to the other components of the routine immunization (DTP), have been assayed among infant recipients of our vaccine in the United States and in Sweden. This technology has been extended successfully to poly alpha(2->8) NeuNAc CPs (group B meningococcus, E. coli KI, Pasteurella haemolytica serotype A2) by multipoint attachment of this polymer to proteins at neutral pH. It was found that a cross-reactive E. coli polysaccharide, K92, elicited antibodies to this and to the related group C meningococcus CP. This technique was also extended to the CP of Cryptococcus neoformans serogroup A. More detailed studies of the conjugation procedure have revealed more effective """"""""spacer"""""""" arms for both this conjugate and for Staphylococcus aureus CP bound to the recombinant Pseudomonas exoprotein A. Conjugates of these vaccines showed increased immunogenicity and T-cell dependent properties in mice. Further, the S. aureus type 5 polysaccharide, bound to the recombinant protein, has been successfully evaluated in phase 1 human studies.
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