SYNTHETIC CLYCO-CONJUGATE VACCINE AGAINST MENINGOCOCCI

THE OBJECTIVE OF PHASE I IS TO PREPARE SYNTHETIC GLYCO-CONJUGATE VACCINES AGAINST MENINGOCOCCAL DISEASES CAUSED BY NEISSERIA MENINGOCOCCI SEROGROUPS A AND C. N. MENINGITIDIS IS A LEADING CAUSE OF BACTERIAL MENINGITIS IN INFANTS, YOUNG ADULTS, AND IN ENCLOSED POPULATIONS SUCH AS IN MILITARY POSTS, SCHOOLS, PRISONS, AND ISOLATED COMMUNITIES. IN THIRD WORLD COUNTRIES, IT CAUSES FREQUENT, SEVERE, AND LONG-LASTING EPIDEMICS. ALTHOUGH THE INCIDENCE OF MENINGOCOCCAL DISEASE IS LOW IN THE UNITED STATES, THE RAPID ONSET OF ILLNESS AND THE SIGNIFICANT MORBIDITY AND MORTALITY ASSOCIATED WITH IT MAKES MENINGOCOCCUS ONE OF THE FASTEST KILLERS OF HUMANS AMONG INFECTIOUS AGENTS. EXISTING MENINGOCOCCAL CAPSULAR POLYSACCHARIDE VACCINES HAVE LIMITED EFFECTIVENESS IN YOUNG CHILDREN AND INFANTS AND INDUCE ONLY SHORT-TERM IMMUNITY, EVEN IN ADULTS. CURRENT RESEARCH IS FOCUSED ON THE DEVELOPMENT OF OLIGOSACCHARIDE-PROTEIN CONJUGATES AS ALTERNATIVE VACCINES. THIS PROJECT INVOLVES PRODUCING OLIGOSACCHARIDES OF WELL-DEFINED CHAIN LENGTH AND COVALENTLY COUPLING THEM TO THE NONTOXIC MUTANT DIPHTHERIA TOXIN CRM197 TO FORM THE GLYCO-CONJUGATE VACCINE. THE PHYSICOCHEMICAL PROPERTIES OF THESE GLYCO-CONJUGATE VACCINES WILL BE EVALUATED BY VARIOUS ANALYTICAL METHODS, AND THEIR IMMUNOGENICITY WILL BE DETERMINED BY VACCINATION OF LABORATORY ANIMALS. THE RESULTS OF THIS RESEARCH WILL BEUSED TO ASSESS THE POTENTIAL FOR PRODUCING A COST-EFFECTIVE,INJECTABLE VACCINE AGAINST MENINGOCOCCAL INFECTIONS.