HUMAN IMMUNE RESPONSE TO POLYSACCHARIDE-PROTEIN CONJUGATE VACCINES

血友病的年龄相关性和t非依赖性免疫特性

The age- related and T-independent immunologic properties of Haemophilus influenzae type b capsular polysaccharide and other polysaccharides of invasive bacteria limit their protective actions as vaccines in infants and children, the age group with the highest attack rate of disease due to these pathogens. A general organic synthetic scheme, that could bind H. influenzae type b and other capsular polysaccharides to carrier proteins was devised in order to both increase the immunogenicity of and confer T-cell dependence (booster effect) to these protective antigens. Based upon our, and the work of others, a conjugated Hib vaccine prepared by our original method was licensed by the FDA for universal use in children greater than 18 months of age. Now, a license has been extended to other conjugates and the postmarketing surveillance success of these new products has lowered the age limits to 15 months of age. We have shown that our H. influenzae type b-tetanus toxoid conjugate is both safe and immunogenic in infants at ages 3, 5, 7 and 18 months of age (recommended schedule for infant vaccines). About 75% of the infants developed protective levels of antibody with one injection and all were protected after the third injection. Protective levels of antibodies were induced to the carrier protein as well. This technology has been extended to Streptococcus group B type III, Cryptococcus neoformans and to group B meningococcus capsular polysaccharide which, heretofore, has been considered nonimmunogenic. High levels of antibodies to this polymer were induced by this conjugate in mice. Two lots of pneumococcus type 12F-DT conjugate evaluated in adult volunteers were found to be safe and induce higher levels of type 12F antibodies than the unconjugated CP vaccine. The lot made with the higher MW CP induced higher antibody levels. Conjugates of staphylococcal types 5 or 8 and Pseudomonas aeruginosa exotoxin A showed increased immunogenicity and T-cell dependent properties in mice.