The objective of the Phase I research is to prepare synthetic glyco- conjugate vaccines against meningococcal diseases caused by N. meningococci serogroups A & C. Neisseria meningitidis is a leading cause of bacterial meningitis in infants, young adults, and in closed populations such as military post, schools, prisons, and isolated communities. In third world countries, it causes frequent, severe epidemics, often running from 3 to 6 years in duration. 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 as 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 short-term immunity, even in adults. Current research developments are focused on the development of oligosaccharide-protein conjugates as alternative vaccines. The 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 physico-chemical 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 be used to assess the potential for producing a cost-effective injectable vaccine which is protective against meningococcal infections.
