HUMAN-ANTIBODY RESPONSES TO MENINGOCOCCAL OUTER-MEMBRANE ANTIGENS AFTER 3 DOSES OF THE NORWEGIAN GROUP-B MENINGOCOCCAL VACCINE

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 Sears 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 (SEA) 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 SEA titer, After 6 months, the GM of Ige 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 SEA 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 Ige; 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 SEA and linear multiple regression analyses indicated that among the major OMPs, antibodies to the Ope 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 SEA response against a strain lacking both the Ope and the class 1 proteins, Three doses converted almost all subjects to SEA 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.