DEVELOPMENT OF GROUP B STREPTOCOCCAL CONJUGATE VACCINES

GROUP B STREPTOCOCCAL INFECTIONS ARE A LEADING CAUSE OF NEONATAL SEPSIS. THIS INCIDENCE OF INVASIVE INFECTIONS DURING THE FIRST TWO MONTHS OF LIFE IS APPROXIMATELY 2-3 CASES PER 1000 LIVE BIRTHS. DESPITE ADVANCES IN DIAGNOSIS, SUPPORTIVE CARE AND TREAMENT, MORTALITY AND MORBIDITY FROM THESE INFECTIONS CONTINUE TO BE SUBSTANTIAL. OF THE FOUR CAPSULAR TYPES, TYPE III STRAINS ACCOUNT FOR ABOUT TWO THIRDS OF THE ISOLATES ASSOCIATES WITH INVASIVE NEONATAL INFECTIONS. IT IS ESTABLISHED IN THE LITERATURE THAT HUMAN IMMUNITY TO GROUP B STREPTOCOCCI CORRELATES WITH TYPE-SPECIFIC ANTICAPSULAR ANTIBODIES. BACTERIAL CAPSULAR POLYSACCHARIDES (CPS), IN GENERAL, ARE POOR AND T-CELL INDEPENDENT IMMUNOGENS. IN MANY CASES, THE POOR IMMUNOGENICITY OF THESE CPS WAS IMPROVED BY THE PRODUCTION OF CONJUGATED VACCINES. COVALENTLY BINDING CPS TO CARRIER PROTEINS MADE THEM BETTER IMMUNOGENS AS EVIDENCED BY ELICITING HIGHER NATIBODY LEVELS, AND T-CELL DEPENDENT IMMUNE RESPONSE. PRELIMINARY RESULTS SHOWED THAT TYPES III, II IA AND IB CPS ARE RELATIVELY POOR IMMUNOGENS WHEN ADMINISTERED TO NORMAL HEALTHY ADULT HUMAN VOLUNTEERS. THIS RESEARCH IS FOR THE PURIFICATION OF TYPE III CPS AND THE PREPARATION OF DIFFERENT CONJUGATES WITH DIFFERENT CARRIER PROTEINS. EACH CONJUGATE WILL BE CHEMICALLY, PHYSICALLY AND IMMUNOLOGICALLY CHARACTERIZED. OPTIMAL CONDITIONS FOR THE PRODUCTION OF THE VACCINES WILLBE ESTABLISHED. MOREOVER, THE BIOLOGICAL ACTIVITY OF THE ANTIBODIES ELICITED BY THE CONJUGATED VACCINE WILL BE EVALUATED IN AN IN-VITRO OPSONOPHAGOCYTOSIS ASSAYS.