Antibodies to meningococcal class 1 outer-membrane protein and its variable regions in patients with systemic meningococcal disease

Abstract

Summary. Antibodies to the meningococcal serosubtype-specific P1.7,16 protein and its variable regions (VR) were analysed in 28 convalescent sera drawn 8-36 months after systemic meningococcal disease by immunoblotting and enzyme immunoassay (EIA) methods. EIA antigens were the meningococcal P1.7,16 protein, produced in Bacillus subtilis, and peptides covering its VRl (P1.7 region) and VR2 (P1.16 region) inserted into a bacterial penicillinase protein. In the immunoblotting method, three meningococcal reference strains were used; they expressed either the P1.7,16 protein, or only its VR1 or VR2 epitopes in their class 1 proteins. Both methods showed a strong IgG response in four sera to P1.7,16 and VR2, but not to VR1; 18 sera had no or weak anti-class 1 protein activity. The six remaining sera were positive only on blots. The VR2-specific sera had 30-fold higher bactericidal activity than those with negligible P1.7,16 responses. Previous vaccination of the patients with a B : 1 5 : P1.7,16 meningococcal vaccine was associated with a strong anti-P 1.7,16 and anti-VR2 booster response that declined with time. The subtype-specific antibody activity in some sera indicated colonisation after disease by meningococci with class 1 proteins different from the strain that had caused disease.

Functional and Specific Antibody Responses in Adult Volunteers in New Zealand Who Were Given One of Two Different Meningococcal Serogroup B Outer Membrane Vesicle Vaccines

“…The variable regions 1 (VR1's) of the two PorA antigens (the P1.7-2 and P1.7 epitopes) are the same except for a deletion of three amino acids in P1.7-2, masking this epitope from interacting with a P1.7-specific monoclonal antibody (35,60), whereas the two VR2's (the P1.4 and P1.16 epitopes) are very different (35). Studies performed by the use of various antibody assays, including immunoblotting, have demonstrated that PorA antibodies induced by MenBvac, MeNZB, or the corresponding PorA components in the Dutch PorA OMV vaccines are mainly directed against VR2 in P1.7,16 and P1.7-2,4 PorA (26,34,42,55,62,63). The VR1 epitopes seem to be less immunogenic than VR2.…”

“…PorA is a key antigen for the bactericidal responses of OMV vaccines, but OpcA and LPS also induce such activity in humans (22,26,34,37,42,43,54,61,66). In the present study, the levels of IgG to these three antigens, in addition to those to PorB and RmpM, in the MenBvac group correlated statistically with SBA against strain 44/76-SL, while only OpcA antibodies showed a corresponding relation with SBA against the homologous strain in the MeNZB vaccinees.…”

Prospects for Vaccine Prevention of Meningococcal Infection

“…For example, one of the antigens that has been targeted for serogroup B vaccines is PorA, an immunogenic outer membrane protein that serves as the basis for the meningococcal serosubtyping system. PorA both is highly variable in strains causing endemic disease and plays a major role in eliciting strain-specific SBAs following nasopharyngeal carriage, invasive meningococcal infection, and serogroup B outer membrane vesicle immunization (177,191,262,297,339,363). Therefore, serogroup B vaccines that use outer membrane vesicles must be polyvalent.…”

Immunization with recombinant class I outermembrane protein from Neisseria meningitidis: influence of liposomes and adjuvants on antibody avidity, recognition of native protein and the induction of a bactericidal immune response against meningococci

“…The class 1 porin appears to be particularly effective in generating a bactericidal immune response following infection (Idanpaan-Heikkila et al, 1995), and the bactericidal activity in sera from humans immunized with experimental vaccines appears largely to be associated with the production of anti-class 1 protein antibodies (Wedege & Froholm, 1986;Milagres et al, 1994;Rosenqvist et al, 1995;van der Voort et al, 1996). Therefore, the class 1 porin is regarded as the most promising candidate for inclusion in new vaccines, and is the basis of a multivalent O M V vaccine (van der Ley et al, 1995) which has undergone phase I trials in adult human volunteers (Peeters et al, 1996).…”