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ENINGOCOCCAL DISEASE caused predominantly by Neisseria meningitidis serogroups A, B, and C occurs predominantly in young children and remains a substantial cause of morbidity and mortality worldwide. 1,2 In addition to causing endemic disease globally, meningococci, unlike other encapsulated bacteria, cause epidemics. Serogroup B epidemics, problematic in Norway and throughout much of Latin America in the 1980s and 1990s, 1 have recently emerged in New Zealand 3 and the United States. [4][5][6] Response to serogroup B epidemics, unlike serogroup A and C epidemics, is difficult because existing serogroup B vaccines have not been shown to be efficacious on an international scale. [7][8][9][10] Quadrivalent meningococcal polysaccharide vaccine is efficacious against meningococcal disease caused by the A, C, W-135, and Y serogroups. [11][12][13] Serogroup B polysaccharide antigen, however, is poorly immunogenic in humans, 14,15 and the elicitation of antibodies to serogroup B polysaccharide antigen is of concern because this antigen is present in human neonatal neural tissue. 16,17 Therefore, alternative Author Affiliations are listed at the end of this article.

The utility of wild-type outer membrane vesicle (wtOMV) vaccines against serogroup B (MenB) meningococcal disease has been explored since the 1970s. Public health interventions in Cuba, Norway and New Zealand have demonstrated that these protein-based vaccines can prevent MenB disease. Data from large clinical studies and retrospective statistical analyses in New Zealand give effectiveness estimates of at least 70%. A consistent pattern of moderately reactogenic and safe vaccines has been seen with the use of approximately 60 million doses of three different wtOMV vaccine formulations. The key limitation of conventional wtOMV vaccines is their lack of broad protective activity against the large diversity of MenB strains circulating globally. The public health intervention in New Zealand (between 2004–2008) when MeNZB was used to control a clonal MenB epidemic, provided a number of new insights regarding international and public-private collaboration, vaccine safety surveillance, vaccine effectiveness estimates and communication to the public. The experience with wtOMV vaccines also provide important information for the next generation of MenB vaccines designed to give more comprehensive protection against multiple strains.

Serum bactericidal activity (SBA) and ELISA antibody levels elicited by two efficacious serogroup B meningococcal vaccines were measured in a controlled trial involving 408 15- to 20-year-olds. Subjects were given two doses at a 6-week interval of a serogroup B or control vaccine. Response was defined as > or = 4-fold rise in antibody level. After two doses of the Finlay Institute (Havana) vaccine at 12 months, the proportions of SBA and ELISA responders were not different from those of the control group (15% and 17% [vaccine] vs. 13% and 9% [control], P > .05). After two doses of the National Institute of Public Health (Oslo) vaccine, there were more SBA and ELISA responders than in the control group (47% and 34% [vaccine] vs. 10% and 1% [control]) or the Finlay Institute vaccine group (P < .05 for both). SBA and ELISA may be insensitive correlates for protective efficacy for some outer membrane protein-based serogroup B meningococcal vaccines.

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