Human IgG subclass responses in relation to serum bactericidal and opsonic activities after immunization with three doses of the Norwegian serogroup B meningococcal outer membrane vesicle vaccine.

Ten adult volunteers, with low prevaccination levels of serum IgG antibodies against meningococcal antigens (< 1 microg ml(-1)), received three doses of the Norwegian group B meningococcal outer membrane vesicle (OMV) vaccine intramuscularly at weeks 0, 6 and 46. Anti-OMV IgG subclass responses were measured and compared with serum bactericidal activity (SBA) and opsonic activity against the vaccine strain 44/76. All vaccinees showed an IgG1 antibody response after each vaccine dose. The vaccine-induced median serum IgG1 antibody levels were 16, 17 and 18 microg ml(-1) 2-6 weeks after the first, second and third dose, respectively. Three vaccinees showed a weak IgG3 response after the first dose, whereas 8 and 9 showed a response after the second (median = 10 microg ml(-1)) and third dose (median = 10 microg ml(-1)), respectively. Low levels of anti-OMV IgG2 antibodies were found, whilst specific IgG4 antibodies were only detected for one vaccinee. The vaccine induced at least a fourfold increase in SBA titre in 8 vaccinees after the first dose, in 9 vaccinees after 2 doses and in all vaccinees after 3 doses. A positive correlation was found between IgG1 subclass antibody levels and SBA (r = 0.62, P < 0.0001). Elevated opsonophagocytic activity, measured as respiratory burst (RB), was observed in all vaccinees after one vaccine dose and usually increased after 2 and 3 doses. A strong positive correlation was found between IgG1 antibody levels and RB (r = 0.76, P < 0.0001). In conclusion, we have shown that systemic meningococcal OMV vaccination in adult vaccinees mainly induced IgG1 antibodies which correlated with bactericidal and opsonic activity, but also a considerable amount of IgG3 antibodies, which, in contrast to the IgG1 response, was induced only after 2 or 3 vaccine doses and declined more rapidly.