RESUMO
A native outer membrane vesicles (NOMV) vaccine was developed from three antigenically diverse strains of Neisseria meningitidis that express the L1,8, L2, and L3,7 lipooligosaccharide (LOS) immunotypes, and whose synX, and lpxL1 genes were deleted.. Immunogenicity studies in mice showed that the vaccine induced bactericidal antibody against serogroups B, C, W, Y and X N. meningitidis strains. However, this experimental NOMV vaccine was not effective against serogroup A N. meningitidis strains. N. meningitidis capsular polysaccharide (PS) from serogroups A, C, W and Y were effective at inducing bactericidal antibody when conjugated to either tetanus toxoid or the fHbp1-fHbp2 fusion protein fHbp(1+2). The combination of the NOMV vaccine and the N. meningitidis serogroup A capsular polysaccharide (MAPS) protein conjugate was capable of inducing bactericidal antibodies against a limited number of N. meningitidis strains from serogroups A, B, C, W, Y and X tested in this study.
Assuntos
Vacinas Meningocócicas/imunologia , Neisseria meningitidis/imunologia , Animais , Antígenos de Bactérias/genética , Antígenos de Bactérias/imunologia , Proteínas da Membrana Bacteriana Externa/genética , Proteínas da Membrana Bacteriana Externa/imunologia , Reações Cruzadas/imunologia , Citocinas/sangue , Endotoxinas/metabolismo , Meningite Meningocócica/metabolismo , Meningite Meningocócica/prevenção & controle , Vacinas Meningocócicas/genética , Camundongos , Neisseria meningitidis/classificação , Neisseria meningitidis/genética , Neisseria meningitidis Sorogrupo B/genética , Neisseria meningitidis Sorogrupo B/imunologia , Sorotipagem , Vacinas Conjugadas/genética , Vacinas Conjugadas/imunologiaRESUMO
Rabbit immunogenicity studies on an experimental trivalent native outer membrane vesicle vaccine derived from three serogroup B strains were conducted to evaluate the effectiveness of this vaccine at inducing an antibody response with serum bactericidal activity against meningococcal strains of other serogroups in addition to serogroup B strains. The results showed that the vaccine was capable of inducing an effective broad-based bactericidal antibody response in rabbits against a small sample of Neisseria meningitidis strains of serogroups C, W135, and X and, to a lesser extent, serogroups A and Y. Analysis of antibody specificity using a bactericidal depletion assay revealed that antibodies to lipooligosaccharide (LOS), PorA, and NadA induced in rabbits by the experimental trivalent outer membrane vesicle vaccine were responsible for most of the bactericidal activity against strains of the other N. meningitidis serogroups. In the case of serogroup A N. meningitidis strains, the outer membrane antigen NadA was primarily responsible for protection. The outer membrane antigens fHbp and OpcA were also effective in removing some bactericidal activity from the sera.
Assuntos
Atividade Bactericida do Sangue , Vacinas Meningocócicas/imunologia , Neisseria meningitidis/imunologia , Adesinas Bacterianas/imunologia , Animais , Anticorpos Antibacterianos/sangue , Antígenos de Bactérias/imunologia , Feminino , Lipopolissacarídeos/imunologia , Vacinas Meningocócicas/administração & dosagem , Porinas/imunologia , Coelhos , Vesículas Secretórias/imunologiaRESUMO
A trivalent native outer membrane vesicle vaccine that has potential to provide broad based protection against Neisseria meningitidis serogroup B strains has been developed. Preliminary immunogenicity studies in mice showed that the vaccine was capable of inducing an effective broad based bactericidal antibody response against N. meningitidis serogroup B strains. These findings in mice have been repeated with a cGMP trivalent NOMV vaccine and extended to show that the bactericidal antibody response induced by the vaccine in mice is effective against strains belonging to serogroups C, Y, W135, X, and NadA-expressing serogroup A strains. Taken together these results suggest that this experimental vaccine may provide protection against both serogroup B and non-serogroup B N. meningitidis strains.
Assuntos
Anticorpos Antibacterianos/sangue , Atividade Bactericida do Sangue , Reações Cruzadas , Exossomos/imunologia , Vacinas Meningocócicas/imunologia , Neisseria meningitidis Sorogrupo B/imunologia , Animais , Vacinas Meningocócicas/administração & dosagem , CamundongosRESUMO
A vaccine based on native outer membrane vesicles (NOMV) that has potential to provide safe, broad based protection against group B strains of Neisseria meningitidis has been developed. Three antigenically diverse group B strains of N. meningitidis were chosen and genetically modified to improve safety and expression of desirable antigens. Safety was enhanced by disabling three genes: synX, lpxL1, and lgtA. The vaccine strains were genetically configured to have three sets of antigens each with potential to induce protective antibodies against a wide range of group B strains. Preliminary immunogenicity studies with combined NOMV from the three strains confirmed the capacity of the vaccine to induce a broad based bactericidal antibody response. Analysis of the bactericidal activity indicated that antibodies to the LOS were responsible for a major portion of the bactericidal activity and that these antibodies may enhance the bactericidal activity of anti-protein antibodies.
