Development of vaccines against meningococcal disease.
ABSTRACT 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.
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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.Tropical Medicine & International Health 09/2012; DOI:10.1111/j.1365-3156.2012.03085.x · 2.30 Impact Factor
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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.
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ABSTRACT: Outer membrane vesicles (OMV) are used as a vaccine against Neisseria meningitidis serogroup B and are traditionally produced with detergent-extraction to remove toxic lipopolysaccharide. Engineered strains with attenuated lipopolysaccharide allowed the use of native vesicles (NOMV) with improved stability and immunogenicity. In the NOMV production process detergents are omitted and vesicle release is stimulated with EDTA extraction (a chelating agent) to enable a higher yield. Many process parameters may change the EDTA extraction efficiency, but it is unknown what the optimal ranges for these parameters are in terms of quality. The present study systematically optimized EDTA extraction and was representative for production at large-scale. Two critical process parameters were identified, harvest point of the cultivation (harvest) and pH of the extraction buffer (pH), which significantly affected yield (7-fold) and bacterial lysis (35-fold). The other quality attributes remained unchanged. Optimization of harvest and pH revealed that the desired low bacterial lysis coincided with intermediate but sufficient yield. High functional immunogenicity and low toxicity of the optimized vaccine were also confirmed. The EDTA extraction is therefore a robust process step which produces high quality OMV if harvest and pH are controlled accurately.Vaccine 03/2012; 30(24):3683-90. DOI:10.1016/j.vaccine.2012.03.028 · 3.49 Impact Factor