BACTERICIDAL ANTIBODY-RESPONSES OF JUVENILE RHESUS-MONKEYS IMMUNIZED WITH GROUP-B NEISSERIA-MENINGITIDIS CAPSULAR POLYSACCHARIDE-PROTEIN CONJUGATE VACCINES

Reports on the bactericidal activities of antibodies to group B Neisse ria meningitidis capsular polysaccharide (B PS) are conflicting, Using three different complement sources, we analyzed the bactericidal acti vities of sera of juvenile rhesus monkeys immunized with five conjugat e vaccines of B PS synthesized by different schemes, an Escherichia co li K92 conjugate, and a noncovalent complex of B PS with group B menin gococcal outer membrane vesicles (B+OMV) (S. J. N. Devi, W. D. Zolling er, P. J. Snoy, J. Y. Tai, P. Costantini, F. Norelli, R. Rappuoli, and C. E. Frasch, Infect. Immun. 65:1045-1052, 1997). With rabbit complem ent, nearly all preimmune sera showed relatively high bactericidal tit ers, and all vaccines, except the K92 conjugate, induced a fourfold or greater increase in bactericidal titers in most of the monkeys vaccin ated, In contrast, with human complement, most prevaccination sera sho wed no bactericidal activity and in most of the vaccine groups, little or no increase in bactericidal titer was observed, However, the coval ent conjugation of P BS and OMV (B-OMV) administered with and without the Ribi adjuvant induced relatively high bactericidal titers which pe rsisted up to 30 weeks, An analysis of the specificities of bactericid al antibodies revealed that absorption with E. coli K1 cells did not c hange the bactericidal titer with human complement but reduced the tit ers observed with the rabbit and monkey complements, A significant inc rease in anti-lipopolysaccharide (LPS) antibodies was elicited by the B-OMV conjugates, and nearly all of the bactericidal activity with hum an complement could be inhibited with the purified group B meningococc al L3,7,8 LPS. B-OMV covalently coupled via adipic acid dihydrazide el icited significantly elevated levels (P less than or equal to 0.02) of anti-OMV antibodies compared to those of the noncovalently complexed B+OMV, An initial small-scale evaluation of B PS conjugates in adult h uman males appears feasible, with careful monitoring, to settle the in consistent reports of the importance of source of complement in elicit ing bacteriolysis, Subsequent analysis of resultant human antibodies f or bacteriolysis, opsonophagocytosis, and protective efficacy in anima l models may be the first step toward answering safety-and efficacy-re lated concerns about B PS conjugate vaccines.