Immune response of Brazilian children to a Neisseria meningitidis serogroup B outer membrane protein vaccine: comparison with efficacy

Since 1986, serogroup B Neisseria meningitidis has caused approximately 80% of the meningococcal disease in Brazil. In 1988, an epidemic caused by N. meningitidis B:4:P1.15 was recognized in the greater São Paulo area of Brazil. The São Paulo state government decided to vaccinate children from 3 to 83 months of age with a vaccine consisting of serotype 4 outer membrane protein and group C meningococcal polysaccharide that was produced in Cuba. About 2.7 million children were vaccinated during two immunization campaigns conducted in 1989 and 1990. Because of this, a case-control study was designed to determine vaccine efficacy against group B meningococcal disease. The purpose of our study was to compare the antibody response with the protection from disease estimated from the case-control study. We measured the immune responses of vaccinees by enzyme-linked immunosorbent assay (ELISA), immunoblot, and bactericidal assay. The development of bactericidal antibodies was age dependent and in good agreement with the results of the case-control study. Only 40% of vaccinees showed fourfold or greater increases in bactericidal antibody titers after vaccination. A poor correlation between antibody levels detected by ELISA and those by bactericidal assay was found. Immunoblot analysis showed that about 50% of the serum samples with bactericidal titers higher than 1:4 were reactive with class 1 outer membrane protein. We conclude that the bactericidal assay is a good, laboratory-based, functional assay for the study of vaccine immunogenicity and that an effective solution to group B meningococcal disease remains to be demonstrated.