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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.

Vaccines based on outer membrane vesicles (OMV) were developed more than 20 years ago against Neisseria meningitidis serogroup B. These nano-sized structures exhibit remarkable potential for immunomodulation of immune responses and delivery of meningococcal antigens or unrelated antigens incorporated into the vesicle structure. This paper reviews different applications in OMV Research and Development (R&D) and provides examples of OMV developed and evaluated at the Finlay Institute in Cuba. A Good Manufacturing Practice (GMP) process was developed at the Finlay Institute to produce OMV from N. meningitidis serogroup B (dOMVB) using detergent extraction. Subsequently, OMV from N. meningitidis, serogroup A (dOMVA), serogroup W (dOMVW), and serogroup X (dOMVX) were obtained using this process. More recently, the extraction process has also been applied effectively for obtaining OMV on a research scale from Vibrio cholerae (dOMVC), Bordetella pertussis (dOMVBP), Mycobacterium smegmatis (dOMVSM), and BCG (dOMVBCG). The immunogenicity of the OMV has been evaluated for specific antibody induction, and together with functional bactericidal and challenge assays in mice has shown their protective potential. dOMVB has been evaluated with non-neisserial antigens, including with a herpes virus type 2 glycoprotein, ovalbumin, and allergens. In conclusion, OMV are proving to be more versatile than first conceived and remain an important technology for development of vaccine candidates.