Inching toward a serogroup B meningococcal vaccine for infants.

JAMA The Journal of the American Medical Association (Impact Factor: 30.39). 02/2012; 307(6):614-5. DOI: 10.1001/jama.2012.118
Source: PubMed
  • Vaccine 01/2014; 32(9). DOI:10.1016/j.vaccine.2013.12.066 · 3.49 Impact Factor
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    ABSTRACT: Meningococcal disease is a life-threatening invasive infection (mainly septicemia and meningitis) that occurs as epidemic or sporadic cases. The causative agent, Neisseria men-ingitidis or meningococcus, is a capsulated Gram-negative bacterium. Current vaccines are prepared from the capsular polysaccharides (that also determine serogroups) and are available against strains of serogroups A, C, Y, and W-135 that show variable distribution worldwide. Plain polysaccharide vaccines were first used and subsequently conjugate vaccines with enhanced immunogenicity were introduced. The capsular polysaccharide of meningococcal serogroup B is poorly immunogenic due to similarity to the human neural cells adhesion molecule. Tailor-made, strain-specific vaccines have been developed to control localized and clonal outbreaks due to meningococci of serogroup B but no "universal" vaccine is yet available. This unmet medical need was recently overcome using several subcapsular proteins to allow broad range coverage of strains and to reduce the risk of escape variants due to genetic diversity of the meningococ-cus. Several vaccines are under development that target major or minor surface proteins. One vaccine (Bexsero ® ; Novartis), under registration, is a multicomponent recombinant vaccine that showed an acceptable safety profile and covers around 80% of the currently circulating serogroup B isolates. However, its reactogenicity in infants seems to be high and the long term persistence of the immune response needs to be determined. Its activity on carriage, and there-fore transmission, is under evaluation. Indirect protection is expected through restricting strain circulation and acquisition. This vaccine covers the circulating strains according to the presence of the targeted antigens in the circulating isolates as well as to their levels of expression. The coverage rate should therefore be updated and the surveillance of circulating isolates should include typing schemes for the antigens of the future vaccines. We review the recent available data for these upcoming protein-based vaccines and particularly Bexsero ® .
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    ABSTRACT: Factor H binding protein (fHbp) is a principal antigen in a multicomponent meningococcal vaccine recently licensed in Europe for prevention of serogroup B diseases. The protein recruits the complement down-regulator, factor H (fH), to the bacterial surface, which enables the organism to resist complement-mediated bacteriolysis. Binding is specific for human fH. In preclinical studies, mice and rabbits immunized with fHbp vaccines developed serum bactericidal antibody responses, which in humans predict protection against developing meningococcal disease. These studies, however, were in animals whose fH did not bind to the vaccine antigen. Here we review the immunogenicity of fHbp vaccines in human fH transgenic mice. The data suggest that animals with high serum human fH concentrations have impaired protective antibody responses. Further, mutant fHbp vaccines with single amino acid substitutions that decrease fH binding are superior immunogens, possibly by unmasking epitopes in the fH binding site that are important for eliciting serum bactericidal antibody responses. Humans immunized with fHbp vaccines develop serum bactericidal antibody but achieving broad coverage in infants required incorporating additional antigens including outer membrane vesicles, which increased rates of fever and local reactions at the injection site. The experimental results in transgenic mice predict that fHbp immunogenicity can be improved in humans by using mutant fHbp vaccines with decreased fH binding. These results have important public health implications for developing improved fHbp vaccines for control of serogroup B meningococcal disease, and for development of vaccines against other microbes that bind host molecules.
    Clinical and vaccine Immunology: CVI 06/2013; 20(8). DOI:10.1128/CVI.00260-13 · 2.37 Impact Factor