Functional Activities and Epitope Specificity of Human and Murine Antibodies against the Class 4 Outer Membrane Protein (Rmp) of Neisseria meningitidis

Abstract

Antibodies against the class 4 outer membrane protein (OMP) fromNeisseria meningitidis have been purified from sera from vaccinees immunized with the Norwegian meningococcal group B outer membrane vesicle vaccine. The human sera and purified antibodies reacted strongly with the class 4 OMP in immunoblots, whereas experiments with whole bacteria showed only weak reactions, indicating that the antibodies mainly reacted with parts of the class 4 molecule that were not exposed. The purified human anti-class 4 OMP antibodies and the monoclonal antibodies (MAbs) were neither bactericidal nor opsonic against live meningococci. Three new MAbs against the class 4 OMP were generated and compared with other, previously described MAbs. Three linear epitopes in different regions of the class 4 OMP were identified by the reaction of MAbs with synthetic peptides. The MAbs showed no blocking effect on bactericidal activity of MAbs against other OMPs. However, one of the eight purified human anti-class 4 OMP antibody preparations, selected from immunoblot reactions among sera from 27 vaccinees, inhibited at high concentrations the bactericidal effect of a MAb against the class 1 OMP. However, these antibodies were not vaccine induced, as they were present also before vaccination. Therefore, this study gave no evidence that vaccination with a meningococcal outer membrane vesicle vaccine containing the class 4 OMP induces blocking antibodies. Our data indicated that the structure of class 4 OMP does not correspond to standard β-barrel structures of integral OMPs and that no substantial portion of the OmpA-like C-terminal region of this protein is located at the surface of the outer membrane.

Antigenic cross-reactivity between outer membrane proteins of Neisseria meningitidis and commensal Neisseria species

“…The other major antigen common to all N. meningitidis and N. lactamica strains, also recognised by all sera, has an apparent molecular mass of approximately 32 kDa and is not regulated by iron levels. This antigen could be the meningococcal class 4 protein, exhaustively studied because it is antigenically invariant and able to induce antibodies that block the bactericidal activity of other antibodies, although this activity has recently been questioned [31]. The class 4 protein has a molecular mass between 32 and 34 kDa, but it is not clear that the meningococcal class 4 proteins have antigenic cross-reactivity with N. lactamica strains [32].…”

Molecular mimetics of polysaccharide epitopes as vaccine candidates for prevention of Neisseria meningitidis serogroup B disease

“…These include vaccines based on eliciting antibody to the group B capsule [22,23] or to non-capsular antigens. The non-capsular approaches include outer membrane vesicle (OMV) vaccines [24^27], speci¢c outer membrane proteins (OMPs) such as PorA [28^34], iron-regulated proteins [35^37], class 4 (Rmp) proteins [38], Opc [39], Neisserial surface protein A [40,41] and detoxi¢ed lipopolysaccharide [42^46]. In this minireview, we summarize the status of some of the more promising and/or clinically advanced approaches for development of a meningococcal B vaccine.…”

Differential Capacities of Outer Membrane Proteins from Neisseria meningitidis B to Prime the Murine Immune System after Vaccination

“…It has been described that mouse MoAb to RmpM can block bactericidal killing by anti-PorA MoAb [19]. Nevertheless, an elegant study by Rosenqvist et al [20] showed no blocking effect on bactericidal activity of MoAb anti-RmpM or immunoglobulin (Ig) anti-RmpM purified from serum of vaccinees. Of note, the human Ig anti-RmpM preparations were obtained from sera collected after two doses of the Norwegian Men B vaccine.…”