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Prevalence And Genetic Diversity Of Candidate Vaccine Antigens Among Neisseria Meningitidis Isolates In China

Posted on:2013-12-21Degree:MasterType:Thesis
Country:ChinaCandidate:H L YangFull Text:PDF
GTID:2284330467451814Subject:Pathogen Biology
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Meningococcal meningitis and septicaemia can be a life threatening disease caused by the Gram-negative bacterium, Neisseria meningitidis. Based on the immunochemistry of the capsular polysaccharide, Neisseria meningitidis can be classified into one of12serogroups. Serogroups A, B, C, Y, W135and X are responsible for the majority of meningococcal disease globally. Nongroupable meningococci are common in the human nasopharynx.The most effective prevention strategy for meningococcal disease is vaccinization. Meningococcal polysaccharide or polysaccharide-protein conjugate vaccines against serogroup A, C, W135, and Y have become available, prevention of meningococcal.The MenB (Serogroup B Meningococcus) capsular polysaccharide is poorly immunogenic as it is antigenically similar to the human foetal neural cell adhesion molecule. The MenB capsular polysaccharide is not suitable to the development of MenB vaccine.Therefore, researchers have focused the search for candidate vaccine antigens on protein targets. Reverse vaccinology was first successfully used by Novartis Vaccines to develop a novel MenB vaccine using the genome from the MenB strain MC58. These antigens include Factor H binding protein (FHbp), Neisserial adhesin A (NadA,), Neisserial heparin-binding Antigen (NhbA), GNA2091and GNA1030. These antigens in MenB existed in non-B meningococci.5CVMB may protect against both B and non-B meningococcal disease. The study detected the prevalence of five antigen genes in MenB protein vaccine in210Neisseria meningitidis isolates in China.Sequencing each gene in the different strains will be important to evaluate antigen conservation and assortment and to allow a future prediction of potential vaccine coverage.fHbp、nhba、gna1030and gna2091were detected in210Neisseria meningitidis isolates. Among210isolates,48isolates harbored nadA gene by PCR and dot blotting. Sequencing fHbp and nadA gene in the different strains will be important to evaluate antigen conservation and assortment.All210isolates contain fHbp、nhba、gna1030and gna2091. Among210isolates,48isolates (48/210,23.3%) harbored nadA. Among48isolates harbored nadA,44isolates belonged to ST-5complex,4isolates belonged to ST-11complex. Based on amino acids,47isolates belonged to NadA V3and1isolates belonged to NadA V4. FHbp has been classified into three variants (1,2and3) in110Neisseria meningitidis isolates.Among the110isolates analyzed by DNA sequencing,49isolates harbored FHbp V1,52belonged to FHbp V2and9belonged to FHbp V3.5CVMB FHbp and NadA variants in Neisseria meningitidis isolates were different in China and other countries. In China,FHbp V1in NmA and NmC isolates was predominant, FHbp V2was predominant in NmB isolates.48isolates harbored NadA concentrated in ST-5complex and ST-11complex. Of44isolates belonged to ST-5complex,37isolates was NmA,7isolates was NmC; Of4isolates belonged to ST-11complex,3isolates was NmW135,1-isolates was NG Nm. The Chinese NmB didn’t harbor NadA. The majority of NmB strains harbor FHbp V1, NadA was detected in NmB and NmC isolates than in other serogroups. FHbp and NadA for Chinese NmA and NmC isolates is effective, but for Chinese NmB isolates is limited. In China, MenB protein vaccines should be based on the antigenic characteristics of Chinese Nm strains.The study optimized the adhesive assay of Neisseria meningitidis. The adhesive ability of meningococcal Group C ST(Sequence Type)-4821complex isolates and nongroupable isolates in Neisseria meningitidis were examined and compared by in vitro infection assays using the larynx carcinoma epithelial cell line HEp-2. Adhesive ability of meningococcal Group C ST-4821complex strains and serogroup nongroupable isolates is differential.
Keywords/Search Tags:Neisseria Meningitidis, factor H binding protein, neisserial adhesin A
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