Human antibody responses to meningococcal outer membrane antigens after three doses of the Norwegian group B meningococcal vaccine

Abstract

The antibody kinetics in sera from 27 adults after three doses of the Norwegian group B meningococcal outer membrane vesicle (OMV) vaccine was studied. The vaccinees received the third dose 4 to 5 years after the first two. Antibody responses against outer membrane proteins (OMPs) and lipopolysaccharides were studied by enzyme-linked immunosorbent assay and immunoblotting and with serum bactericidal assays (SBA) with three variants of the vaccine strain, 44/76. Six weeks after the second injection, the geometric mean (GM) of the levels of immunoglobulin G (IgG) against OMVs was about sevenfold higher than that of prevaccination levels, and 74% of the vaccinees developed a greater-than-twofold rise in SBA titer. After 6 months, the GM of IgG levels declined to about threefold higher, and after 4 to 5 years it declined to about twofold higher, than that before vaccination. The third dose induced a rapid increase in SBA titers in 96% of the vaccinees, and the GM of levels of IgG against OMVs rose to about 14-fold the prevaccination level. One year later, the IgG antibody levels had dropped to 4.6-fold the prevaccination level, but 88% of the vaccinees still showed bactericidal activity. The response after the two first doses was higher in individuals with prevaccination antibodies, but no such effect was found after three doses. The use of defined mutants in SBA and linear multiple regression analyses indicated that among the major OMPs, antibodies to the Opc and class 1 proteins made the most important single contributions to the bactericidal activity against the vaccine strain, but it also demonstrated the importance of antibodies against other antigens. After three doses, 68% of the vaccinees showed a significant SBA response against a strain lacking both the Opc and the class 1 proteins. Three doses converted almost all subjects to SBA responders and gave higher antibody levels and relatively less serosubtype-specific bactericidal activity than did two doses, probably indicating a broader cross-protection against heterologous strains.

Activation of human dendritic cells by the PorA protein of Neisseria meningitidis

“…These data suggest that PorA treatment is likely to induce a Th2-mediated immune response that is necessary for generating humoral antibody responses required for protective immunity against meningococci. This conclusion is consistent with reports of high levels of antibody to PorA protein(s) detected in individuals following colonization with meningococci (Jones et al, 1998;Williams et al, 2003), invasive disease (Guttormsen et al, 1994;Idanpaan-Heikkila et al, 1995) or vaccination with several different OM vesicle vaccines (Rosenqvist et al, 1995;Peeters et al, 1996;van der Voort et al, 1996;de Kleijn et al, 2001).…”

Opa proteins and CEACAMs: pathways of immune engagement for pathogenicNeisseria

“…If Opa does indeed downregulate immune responses in vivo, the deletion of Opa from potential vaccine preparations could improve the immunogenicity of OMVs. Previous clinical trials of OMV vaccines, which contained variable amounts of Opa, have already demonstrated that these vaccines are immunogenic, and that most of the antibody response is directed against PorA (Bjune et al, 1991;Sierra et al, 1991;Rosenqvist et al, 1995;Milagres et al, 1998;Oster et al, 2005Oster et al, , 2007Martin et al, 2006). There is significant variation in anti-Opa antibody responses, both between studies and among individuals within studies (Poolman et al, 1983;Wedege & Froholm, 1986;Mandrell & Zollinger, 1989).…”

Streptococcus pneumoniae heat shock protein 70 does not induce human antibody responses during infection

“…Because PspA is an antigenically variable protein [17], the epitope for mAb 180,C-1 was detected in only 19 out of 76 examined S. pneumoniae strains. The negative control mAb 184,F-12 (IgG3) reacts with the P1.16 epitope on meningococcal class 1 protein [18].…”