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

Abstract

This study presents detailed analyses of total and specific serum antibody levels among 26 and 24 adult volunteers before vaccination and after the third dose of the meningococcal serogroup B outer membrane vesicle (OMV) vaccines MeNZB and MenBvac, respectively, in a clinical trial in New Zealand (V. Thornton, D. Lennon, K. Rasanathan, J. O'Hallahan, P. Oster, J. Stewart, S. Tilman, I. Aaberge, B. Feiring, H. Nokleby, E. Rosenqvist, K. White, S. Reid, K. Mulholland, M. J. Wakefield, and D. Martin, Vaccine 24:1395-1400, 2006). With the homologous vaccine strains as targets, both vaccines induced significant increases in serum bactericidal and opsonophagocytic activities and in the levels of immunoglobulin G (IgG) to OMV antigens in an enzyme-linked immunosorbent assay (ELISA) and to live meningococci by flow cytometry. They also induced high levels of activity against the heterologous strains, particularly in terms of opsonophagocytic activity and IgG binding to live bacteria. The antibody levels with the homologous and heterologous strains in the four assays showed high and significant positive correlations. Specific IgG binding to 10 major OMV antigens in each vaccine was measured by scanning of immunoblots; ELISAs for two antigens, lipopolysaccharide and Neisseria surface protein A (NspA), were also performed. Both vaccines elicited significant increases in IgG binding to all homologous and heterologous OMV antigens except NspA. The total IgG band intensity on the blots correlated significantly with the IgG levels determined by the OMV ELISA and flow cytometry. In conclusion, the results of the various immunological assays showed that both OMV vaccines gave rise to high levels of specific and cross-reacting antibodies.

FIG. 1.

Immunoblots demonstrating IgG binding to OMV antigens from the two vaccine strains of pre- and postvaccination sera from one volunteer immunized with three doses of MeNZB. The nitrocellulose strips were incubated without and with 0.02% Tween 20 in the reagents. Strips 1, 3, 5, and 8 were incubated with prevaccination serum; and strips 2, 4, 6, 7, 9, and 10 were incubated with postvaccination serum from volunteer 1043. OMVs from homologous vaccine strain NZ98/254 were antigens for strips 1, 2, 5, 6, and 7; and the heterologous 44/76-SL OMVs were antigens for strips 3, 4, 8, 9, and 10. The positions of the major OMV antigens are shown on both sides of the panel; X designates IgG binding to an unknown antigen visible only in the presence of Tween 20. Specific L1 LPS bands are seen in strips 2 and 6. Strips 7 and 10 were also incubated with 0.15% Empigen BB reagent, which abolished IgG binding to LPS but increased that to PorA, PorB, and/or OpcA. The Adobe Photoshop 8.0 CS program was used to prepare the figure.