Development of vaccines against meningococcal disease

Vaccine Development and Quality and Safety of Biologicals, World Health Organization, Geneva, Switzerland.
The Lancet (Impact Factor: 45.22). 05/2002; 359(9316):1499-508. DOI: 10.1016/S0140-6736(02)08416-7
Source: PubMed


Neisseria meningitidis is a major cause of bacterial meningitis and sepsis. Polysaccharide-protein conjugate vaccines for prevention of group C disease have been licensed in Europe. Such vaccines for prevention of disease caused by groups A (which is associated with the greatest disease burden worldwide), Y, and W135 are being developed. However, conventional approaches to develop a vaccine for group B strains, which are responsible for most cases in Europe and the USA, have been largely unsuccessful. Capsular polysaccharide-based vaccines can elicit autoantibodies to host polysialic acid, whereas the ability of most non-capsular antigens to elicit broad-based immunity is limited by their antigenic diversity. Many new membrane proteins have been discovered during analyses of genomic sequencing data. These antigens are highly conserved and, in mice, elicit serum bactericidal antibodies, which are the serological hallmark of protective immunity in man. Therefore, there are many promising new vaccine candidates, and improved prospects for development of a broadly protective vaccine for group B disease, and for control of all meningococcal disease.

1 Read
  • Source
    • "Unfortunately, it was not possible to extend this success to serogroup B meningococci [56] as this polysaccharide is poorly immunogenic, probably because of its structural similarity to host polysaccharides that decorate the neural cell adhesion molecule of human foetal tissues [57]. A further concern with this polysaccharide is that effective vaccines may lead to autoimmune reactions [57], and the inclusion of this antigen in vaccine preparations remains controversial and unlikely in the foreseeable future [58]. "
    [Show abstract] [Hide abstract]
    ABSTRACT: The development and implementation of conjugate polysaccharide vaccines against invasive bacterial diseases, specifically those caused by the encapsulated bacteria Neisseria meningitidis, Haemophilus influenzae and Streptococcus pneumoniae, has been one of the most effective public health innovations of the last 25 years. These vaccines have resulted in significant reductions in childhood morbidity and mortality worldwide, with their effectiveness due in large part to their ability to induce long-lasting immunity in a range of age groups. At the population level this immunity reduces carriage and interrupts transmission resulting in herd immunity; however, these beneficial effects can be counterbalanced by the selection pressures that immunity against carriage can impose, potentially promoting the emergence and spread of virulent vaccine escape variants. Studies following the implementation of meningococcal serogroup C vaccines improved our understanding of these effects in relation to the biology of accidental pathogens such as the meningococcus. This understanding has enabled the refinement of the implementation of conjugate polysaccharide vaccines against meningitis-associated bacteria, and will be crucial in maintaining and improving vaccine control of these infections. To date there is little evidence for the spread of virulent vaccine escape variants of the meningococcus and H. influenzae, although this has been reported in pneumococci.
    Philosophical Transactions of The Royal Society B Biological Sciences 08/2013; 368(1623):20120147. DOI:10.1098/rstb.2012.0147 · 7.06 Impact Factor
  • Source
    • "The most effective means of combating meningococcal infection is through vaccination. Early successful vaccines based on the capsular polysaccharide of serogroups A, C, Y and W-135 have been refined by the development of glycoconjugate vaccines, introduced in the late 1990s and now in widespread use (Jodar et al. 2002). No such polysaccharide-based vaccine is licensed for serogroup B because of structural similarities of the serogroup B polysaccharide and that found in certain human tissues (Wyle et al. 1972; Finne et al. 1983), and approaches have been largely based on subcapsular outer membrane antigens. "
    [Show abstract] [Hide abstract]
    ABSTRACT: In the last decade, meningococcal serogroup C conjugate vaccination programs have been demonstrated to be hugely successful with a truly impressive public health impact. In sub-Saharan Africa, with the implementation of an affordable serogroup A conjugate vaccine, it is hoped that a similar public health impact will be demonstrated. Challenges still remain in the quest to develop and implement broadly protective vaccines against serogroup B disease. New, broad coverage vaccines against serogroup B are for the first time becoming available although little is known about their antibody persistence, effectiveness or effect on nasopharyngeal carriage. Enhanced surveillance following any potential vaccine introduction against serogroup B needs to be thoroughly implemented. The future now holds a distinct possibility, globally, for substantially decreasing meningococcal disease, regardless of infecting serogroup. Au cours de la dernière décennie, les programmes de vaccination conjugués avec le méningocoque du sérogroupe C ont démontrés un énorme succès avec un impact véritablement impressionnant sur la santé publique. En Afrique subsaharienne, avec l’implémentation d’un vaccin conjugué du sérogroupe A à prix abordable, il est à espérer qu’un impact similaire sur la santé publique sera démontré. Les défis restent encore dans la quête pour développer et implémenter des vaccins à large protection contre la maladie due au sérogroupe B. De nouveaux vaccins avec une large couverture contre le sérogroupe B deviennent pour la première fois disponibles quoique peu soit connu sur la persistance de leurs anticorps, leur efficacité ou leur effet sur le portage nasopharyngé. Une surveillance accrue après toute introduction d’un vaccin potentiel contre le sérogroupe B devrait être sérieusement implémentée. L’avenir nous réserve maintenant une possibilité distincte, globalement, pour diminuer sensiblement la méningococcie, quel que soit le sérogroupe infectant. Durante la última década, se ha demostrado que los programas de vacunación con la vacuna meningocócica conjugada frente al serogrupo C han sido muy exitosos, con un impacto en salud pública realmente impresionante. En África subsahariana, con la implementación de una vacuna conjugada frente al serogrupo A y asequible, se espera demostrar un impacto similar en salud pública. Los retos continúan en la búsqueda del desarrollo e implementación de vacunas que confieran protección amplia contra la enfermedad causada por el serogrupo B. Nuevas vacunas, con una amplia cobertura frente al serogrupo B, comienzan a estar disponibles por primera vez, aunque se conoce poco sobre la persistencia de anticuerpos y la efectividad o el efecto sobre los portadores nasofaríngeos. Es necesario implementar una vigilancia mejorada tras la introducción de cualquier vacuna potencial contra el serogrupo B. En el futuro ahora se vislumbra una posibilidad clara, a nivel global, de una disminución sustancial de la enfermedad meningocócica, independientemente del serogrupo.
    Tropical Medicine & International Health 09/2012; 17(12). DOI:10.1111/j.1365-3156.2012.03085.x · 2.33 Impact Factor
  • Source
    • "Serogroups A, B, C, W135, and Y account for [95 % of the infections. Capsular polysaccharide or capsular polysaccharide conjugate vaccines are available against serogroup A, C, Y, and W135 strains (Jódar et al. 2002; Morley et al. 2001; Rouphael and Stephens 2012). However, no capsule-based vaccine is available for N. meningitidis serogroup B. The immune system tolerates serogroup B capsular polysaccharide because of its similarity to human carbohydrate a(2 ? "
    [Show abstract] [Hide abstract]
    ABSTRACT: Neisseria meningitidis serogroup B is predom-inantly known for its leading role in bacterial meningitis and septicemia worldwide. Although, polysaccharide con-jugate vaccines have been developed and used successfully against many of the serogroups of N. meningitidis, such strategy has proved ineffective against group B meningo-cocci. Here, we proposed to develop peptide epitope-based vaccine candidates from outer membrane (OM) protein contained in the outer membrane vesicles (OMV) based on our in silico analysis. In OMV, a total of 236 proteins were identified, only 15 (6.4 %) of which were predicted to be located in the outer membrane. For the preparation of specific monoclonal antibodies against pathogenic bacterial protein, identification and selection of B cell epitopes that act as a vaccine target are required. We selected 13 outer membrane proteins from OMV proteins while taking into consideration the removal of cross-reactivity. Epitopia web server was used for the prediction of B cell epitopes. Epitopes are distinguished from non-epitopes by properties such as amino acid preference on the basis of amino acid composition, secondary structure composition, and evolu-tionary conservation. Predicted results were subject to verification with experimental data and we performed string-based search through IEDB. Our finding shows that epitopes have general preference for charged and polar amino acids; epitopes are enriched with loop as a second-ary structure element that renders them flexible and also exposes another view of antibody–antigen interaction.
Show more