Alpha (2->8) polysialic acid (PSA) forms the capsular polysaccharide (CPS) of group B Neisseria meningitidis(GBNM), Escherichia coli K1 (ECK1) and a part of E. coli K92 CPS. PSA is a poorly immunogenic, T- independent, conformationally complex and is associated with pathogenesis and protection in GBNM and ECK1 infections. Its poor immunogenicity is attributed mainly to the presence of PSA in fetal mammalian tissues. Recently, PSA has been rendered immunogenic by covalent coupling with various protein carriers. However, these conjugates hve not been administered into humans, because of concern for possible autoimmune consequences. We therefore evaluated the immunogenicity of 7 different group B meningococcal polysaccharide (GBPS) vaccines in juvenile rhesus monkeys. GBPS non-covalently complexed with OMV (Dr. W. Zollinger), GBPS covalently conjugated to CRM-197 (Dr. R. Rappouli) and to OMP (LBP, DBP), N-propionylated GBPS conjugated to OMP3 (Dr. J. Tai), and K92-TT (LBP, DBP) were used in saline, aluminum hydroxide, stearyl tyrosine or MPL+TDM adjuvants. One year old rhesus were immunized i.m. three times at weeks 0, 6 and 14 and bled at various post-immunization periods.There was variation in antibody responses among individual monkeys. All vaccines except K92-TT elicited a two-fold or greater increase in GBPS antibodies after the first immunization. All vaccines including the K92-TT elicited a rise in GBPS antibodies after the first immunization. All vaccines including the K92-TT elicited a rise in GBPS antibody level of five-fold or more after the third immunization. Most of the antibodies elicited by N-propionylated GBPS-OMP3 vaccines were directed to the N- propionylated GVPS-HSA antigen rather than to native GBPS. The K92-TT conjugate also elicited antibodies to group C meningococcal polysaccharide. High levels of anti-OMP antibodies were elicited by the GBPS-OMP conjugates.Antibodies elicited by GBPS-OMP conjugate administered with and without MPL+TDM were most bactericidal in presence of human and rabbit complements. The vaccine-induced antibodies did not seem to cause any visible safety-related symptoms in the animals.
