PRECLINICAL EVALUATION OF GROUP-B NEISSERIA-MENINGITIDIS AND ESCHERICHIA-COLI K92 CAPSULAR POLYSACCHARIDE-PROTEIN CONJUGATE VACCINES IN JUVENILE RHESUS-MONKEYS

We reported the first use of group B meningococcal conjugate vaccines in a nonhuman primate model (S. J. N. Devi, C. E. Frasch, W. Zollinger , and P. J. Snoy, p. 427-429, in J. S. Evans, S. E. Yost, M. C. J. Mai den, and I. M. Feavers, ed., Proceedings of the Ninth International Pa thogenic Neisseria Conference, 1994), Three different group B Neisseri a meningitidis capsular polysaccharide (B PS)-protein conjugate vaccin es and an Escherichia coli K92 capsular polysaccharide-tetanus toroid (K92-TT) conjugate vaccine are here evaluated for safety and relative immunogenicities in juvenile rhesus monkeys with or without adjuvants, Monkeys were immunized intramuscularly with either B PS-cross-reactiv e material 197 conjugate, B PS-outer membrane vesicle (B-OMV) conjugat e, or N-propionylated B PS-outer membrane protein 3 (N-pr. B-OMP3) con jugate vaccine with or without adjuvants at weeks 0, 6, and 14. A cont rol group of monkeys received one injection of the purified B PS alone , and another group received three injections of B PS noncovalently co mplexed,vith OMV. Antibody responses as measured by enzyme-linked immu nosorbent assay varied among individual monkeys, All vaccines except B PS and the K92-TT conjugate elicited a twofold or greater increase in total B PS antibodies after one immunization, All vaccines, including the K92-TT conjugate, elicited a rise in geometric mean B PS antibody levels of ninefold or more over the preimmune levels following the th ird immunization. Antibodies elicited by N-pr. B-OMP3 and B-OMV conjug ates were directed to the N-propionylated or to the spacer-containing B PS antigens as well as to the native B PS complexed with methylated human serum albumin, None of the vaccines caused discernible safety-re lated symptoms.