發(fā)布時(shí)間：2018-04-12 05:56

  本文選題：腦膜炎奈瑟菌 + 奈瑟菌黏附素A(NadA)�。� 參考：《中國疾病預(yù)防控制中心》2012年碩士論文

【摘要】：腦膜炎奈瑟菌(Neisseria meningitidis, Nm)為革蘭陰性雙球菌,主要引起流行性腦脊髓膜炎(簡稱流腦)和敗血癥。根據(jù)菌體表面莢膜多糖的差異,Nm分為12個(gè)血清群,其中A、B、C、Y、W135和X群是引起全球腦膜炎球菌病的主要血清群,許多菌株血清群不可分,稱為不可分群(Nongroupable,NG)菌株。 流腦是疫苗可以預(yù)防的疾病,莢膜多糖是流腦疫苗的主要抗原成分,目前已有A,C,W135和Y群單價(jià)/多價(jià)的多糖疫苗和多糖-蛋白結(jié)合疫苗,疫苗應(yīng)用降低了流腦的發(fā)病率和死亡率。由于B群腦膜炎奈瑟菌(Serogroup B Meningococcus, MenB)的莢膜多糖免疫原性較弱,并且莢膜多糖的唾液酸結(jié)構(gòu)與人類神經(jīng)細(xì)胞黏附因子具有同源性,免疫接種有可能引起自身免疫,因此,普遍認(rèn)為莢膜多糖不適用于MenB疫苗的研發(fā)。 近年來國際上開展了MenB蛋白疫苗研究工作,通過反向疫苗學(xué)技術(shù)研制出MenB蛋白疫苗5CVMB(5Component Vaccine against Meningococcus B)。5CVMB由五種腦膜炎奈瑟菌抗原成分組成：奈瑟菌黏附素A(NadA)、H因子結(jié)合蛋白(FHbp)、GNA2091、奈瑟菌肝素結(jié)合抗原(NhbA)和GNA1030。 MenB蛋白疫苗5CVMB中5種抗原成分不僅存在于MenB,在非B群Nm菌株中同樣是存在的。MenB蛋白疫苗5CVMB不僅可預(yù)防MenB,對其他血清群的Nm也同樣具有預(yù)防效果,可作為通用疫苗針對不同血清群的Nm進(jìn)行有效預(yù)防。 本研究對我國不同血清群Nm菌株蛋白疫苗抗原基因的分布及氨基酸序列多態(tài)性進(jìn)行研究,以期掌握MenB蛋白疫苗與我國Nm菌株之間的相互覆蓋率。研究結(jié)果顯示,我國不同血清群Nm菌株中均存在fHbp、nhba、gna1030和gna2091四種基因。210株Nm菌株中僅48株含有nadA基因(48/206,23.3%),其中,44株Nm菌株屬于ST-5complex,4株Nm菌株屬于ST-11complex。通過氨基酸序列分析,48株NadA陽性菌株中,NadA變異型3(NadA V3)47株(97.92%)。對110株Nm菌株fHbp基因進(jìn)行測序,49株(44.55%)為FHbp V1,52株(47.27%)為FHbp V2,9株(8.18%)為FHbp V3o 5CVMB中主要抗原成分FHbp和NadA亞型在我國不同血清群Nm菌株中的分布與國外有所不同。在我國A群和C群Nm菌株FHbp以V1為主,而在B群Nm菌株FHbp以V2為主。48株含有NadA的Nm菌株集中在ST-5complex和ST-11complex這兩個(gè)克隆群中。44株ST-5complex Nm菌株中37株為A群,7株為C群；4株ST-11complex Nm菌株中3株為W135群,1株為NG。我國B群Nm菌株中不含有NadA。在美國和歐洲Nm主要的流行血清群B群菌株FHbp以V1為主,NadA常在B群和C群Nm菌株中發(fā)現(xiàn)。5CVMB中主要抗原成分FHbp和NadA對我國A群和C群Nm菌株能夠有效的覆蓋,但對B群Nm菌株覆蓋率有限。因此,MenB蛋白疫苗應(yīng)根據(jù)我國Nm菌株中抗原成分特征進(jìn)行研發(fā)。 本研究建立和優(yōu)化了Nm對HEp-2人喉癌上皮細(xì)胞的黏附實(shí)驗(yàn)方法,檢測了我國主要流行的ST-4821克隆群C群菌株和NG Nm菌株對HEp-2細(xì)胞的黏附能力。初步研究結(jié)果顯示,我國主要流行的ST-4821序列群C群Nm和NGNm菌株對HEp-2細(xì)胞的黏附能力存在差異性
[Abstract]:Neisseria meningitidisis (Nmm) is a gram-negative diplococcus, which mainly causes epidemic meningitis and septicemia.According to the difference of bacterial surface capsular polysaccharides, Nm was divided into 12 serogroups, among them, Acarb Con YW135 and X were the main serogroups causing meningococcal disease worldwide, and many of them were indistinguishable and were called indistinguishable strains of Nongroupable NGN (NongroupableNGstrain).Meningitis is a disease which can be prevented by vaccine, and capsule polysaccharide is the main antigen component of the vaccine. At present, there are polysaccharide vaccine and polysaccharide protein conjugate vaccine of ACCW135 and Y group. The application of the vaccine reduces the morbidity and mortality of meningitis.Because of the weak immunogenicity of capsule polysaccharides of Neisseria meningitidis serogroup B Meningococcus (Menb), and the homology between sialic acid structure of capsule polysaccharide and human neuronal adhesion factor, immunization may cause autoimmunity.It is generally believed that capsular polysaccharide is not suitable for the development of MenB vaccine.In recent years, the research work of MenB protein vaccine has been carried out in the world.The MenB protein vaccine 5CVMB(5Component Vaccine against Meningococcus B).5CVMB was developed by reverse vaccinology. It consists of five antigen components of Neisseria meningitidis: Nisseria nisseria Adhetin Agnad Agna factor H binding protein FHbpPU GNA2091, Neisseria heparin binding antigen NhbAand GNA1030.The five antigenic components of MenB protein vaccine 5CVMB not only exist in Menb, but also exist in non-B group Nm strains. 5CVMB can not only prevent Menb, but also prevent Nm from other serum groups.It can be used as a universal vaccine to prevent Nm from different serum groups.In this study, the distribution and amino acid sequence polymorphism of protein vaccine antigen gene of different serogroup Nm strains in China were studied in order to understand the mutual coverage between MenB protein vaccine and Nm strain in China.The results showed that only 48 of the four Nm strains of FHbpnhbagna1030 and gna2091. 210 contained nadA gene, among which 44 Nm strains belonged to ST-5complex4 Nm strains belonging to ST-11complex. the results showed that there were only 48 Nm strains in different serogroups of China, and only 48 strains of Nm strains containing nadA gene, among them, 44 Nm strains belonged to ST-5complex4 Nm strains, which belonged to ST-11complex.The amino acid sequence of 48 NadA positive strains was analyzed.The fHbp gene of 110 Nm strains was sequenced. 49 strains (44.55) were composed of FHbp V1 (52 strains, 47.27) and 9 strains of FHbp V2 (9 strains, 8.18), which were FHbp V3o.The distribution of the main antigen components FHbp and NadA subtypes of 5CVMB in different serogroup Nm strains in China is different from that in foreign countries.The FHbp of group A and group C Nm in China was mainly V1.While in group B Nm FHbp, V2 was the dominant strain. 48 Nm strains containing NadA were concentrated in the two clone groups of ST-5complex and ST-11complex. 37 of 44 ST-5complex Nm strains were group A, 7 were group C, 4 were ST-11complex Nm, 3 were W135, 1 was NG.NadA was not found in Nm strains of group B in China.In the United States and Europe, the main prevalent serogroup B strain FHbp was V1. The main antigen components FHbp and NadA in group B and group C Nm were found to be able to effectively cover the strains of group A and group C in China.But the coverage of group B Nm was limited.Therefore, Menb protein vaccine should be developed according to the characteristics of antigen components of Nm strains in China.In this study, the adhesion of Nm to HEp-2 human laryngeal carcinoma epithelial cells was established and optimized, and the adhesion ability of ST-4821 clone group C and NG Nm strains to HEp-2 cells was tested.The preliminary results show that the adhesion ability of the main ST-4821 sequence group C group Nm and NGNm strain to HEp-2 cells is different.
【學(xué)位授予單位】：中國疾病預(yù)防控制中心
【學(xué)位級(jí)別】：碩士
【學(xué)位授予年份】：2012
【分類號(hào)】：R392

【參考文獻(xiàn)】

相關(guān)期刊論文 前2條

1 ;Characterization of serogroup C meningococci isolated from 14 provinces of China during 1966—2005 using comparative genomic hybridization[J];Science in China(Series C:Life Sciences);2007年01期

2 ;Proteome Analysis of Neisseria meningitidis Serogroup Strains C Associated with Outbreaks in China[J];Biomedical and Environmental Sciences;2010年04期

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本文編號(hào)：1738453