The presently licensed meningococcal vaccine is a tetravalent capsular polysaccharide vaccine that induces immunity to serogroups A, C, Y, and W-135 but not to group B, which causes nearly half of the meningitis cases in the United States. The purpose of this study was to evaluate the safety and immunogenicity of an intranasal native outer membrane vesicle (NOMV) vaccine prepared from a capsule negative strain of group B of Neisseria meningitidis. In this study all volunteers received the same dose of vaccine, but we evaluated two different immunization schedules and the oropharyngeal and intranasal routes of vaccine delivery, assessed nasal cytology for cellular infiltration, and measured antibody-secreting cells (enzyme-linked immunospot assay [ELISPOT]) as an early marker for systemic immune response. Additionally, both intranasal and serum vaccine-specific antibodies were measured as well as serum bactericidal activity. Four groups with a total of 42 subjects were immunized on days 0, 28, and 56. Group 3 received an additional dose on day 7. Group 2 subjects were immunized both intranasally and oropharyngeally. Meningitis and septicemia from Neisseria meningitidis continue to represent a major worldwide threat. In the United States 2,500 to 3,000 cases of meningococcal disease occur each year. This is associated with significant morbidity, with up to 19% of survivors being left with neurologic sequelae (3). Most of the outbreaks in the United States are caused by serogroups B, C, and Y, with the predominance of cases occurring in young adults and infants. Multistate surveillance conducted between 1992 and 1996 reported 35% serogroup C cases, 32% B cases, and 26% Y cases (12). Serogroup C is responsible for the majority of cases in the adolescent population, whereas cases in infants less than 1 year old are more often due to group B.Presently licensed vaccines are available to immunize against serogroups A, C, Y, and W-135. Unfortunately, a licensed vaccine is not available against group B meningococci. The difficulties in developing a group B vaccine have included the lack of immunogenicity of the purified capsular polysaccharide (10,17). Attempts at improving the immunogenicity have included noncovalent complexing and covalent conjugating of the polysaccharide to proteins. Zollinger et al. demonstrated transient increases in specific immunoglobulin M (IgM) antibodies after noncovalent complexing, but these antibodies were not bactericidal with human complement (18). The covalent conjugate vaccines using unmodified B capsular polysaccharide did not yield any better results and were basically not protective or immunogenic in animals. Chemically modified B polysaccharide conjugated to recombinant meningococcal PorB is immunogenic in animals and induces a relatively high-quality antibody response, including IgG antibodies that are bactericidal with homologous complement, but safety and immunogenicity in humans have not been demonstrated (6).The approach shifted to developing lipopolysaccharide (LPS)-depleted ou...

Earlier studies showed that purified IgG from sera of rabbits immunized with a boiled Escherichia coli J5 (Rc chemotype) whole cell vaccine protected neutropenic rats against gram-negative bacterial sepsis. In the present study, de-O-acylated J5 lipopolysaccharide (J5 DLPS) as a noncovalent complex with Neisseria meningitidis group B outer membrane protein (GBOMP) elicited anti-J5 LPS antibodies in rabbits. IgG prepared from immune rabbit sera protected neutropenic rats against lethal challenge with Pseudomonas aeruginosa 12:4:4 (Fisher Devlin immunotype 6). Sixteen of 26 rats treated with the postimmune serum IgG were protected compared with none of 20 rats treated with the control rabbit serum IgG (P < .001). In vitro binding studies showed binding of anti-J5 IgG to several gram-negative bacteria. These results indicate that a subunit vaccine made of J5 DLPS as a noncovalent complex with GBOMP may protect against gram-negative bacteremia.

No abstract

Over 20 years after the development of the meningococcal A and C vaccines, an effective vaccine against Neisseria meningitidis group B is still lacking. Major obstacles in the development of a B vaccine have been the remarkable capacity of the organism to evade the immune defences of the host and the lack of a predictive animal model. Three group B vaccines based on outer membrane proteins have been, or are currently being, evaluated in field trials. Nevertheless, a number of important questions remain such as the identity of the active components, the degree of efficacy against heterologous group B subtypes, and the duration of protection. In addition, work on a variety of alternative approaches to a group B vaccine is rapidly progressing. Among these are use of chemically modified group B polysaccharide, synthetic or natural lipopolysaccharide epitopes, synthetic peptides corresponding to bactericidal epitopes on the class 1 outer membrane protein, and iron binding proteins. Although each of these approaches has some problems associated with it, the prospects remain good for an effective solution to the group B problem.

No abstract