Protective antibody responses elicited by a meningococcal outer membrane vesicle vaccine with overexpressed genome-derived neisserial antigen 1870
Protective antibody responses elicited by a meningococcal outer membrane vesicle vaccine with overexpressed genome-derived neisserial antigen 1870
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DOI：
10.1086/432102
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发表时间：
2005-08-15
影响因子：
6.4
通讯作者：
Granoff, DM
中科院分区：
文献类型：
--
作者：
Hou, VC;Koeberling, O;Granoff, DM
背景。脑膜炎球菌外膜囊泡（OMV）疫苗对人有效，但有针对孔蛋白PorA的血清亚型特异性血清杀菌抗体反应，并且有可能对PorA逃逸突变体进行免疫选择。我们从脑膜炎奈瑟菌菌株中制备了一种OMV疫苗，该菌株经过工程改造，过表达基因组衍生的奈瑟菌抗原（GNA） 1870，这是一种通过基因组挖掘发现的脂蛋白，正在研究用于疫苗。用改良的GNA1870-OMV疫苗免疫的小鼠比用重组GNA1870蛋白疫苗或由野生型脑膜炎奈菌制备的OMV疫苗或由野生型脑膜炎奈菌和重组蛋白制备的组合疫苗免疫的对照小鼠产生更广泛的血清杀菌抗体应答。经改良的GNA1870-OMV疫苗免疫的小鼠抗血清也能在活的脑膜炎奈雪菌表面产生更多的人C3补体沉积，并在幼鼠中对脑膜炎球菌菌血症具有更强的被动保护活性。PorA表达降低的脑膜炎奈球菌突变体对抗gna1870抗体的杀菌活性更敏感。与重组GNA1870蛋白或传统的OMV疫苗相比，改良的GNA1870-OMV疫苗对脑膜炎球菌病具有更广泛的保护作用，并且与传统的OMV疫苗相比，选择pora逃逸突变体的风险也更小。
Background. Meningococcal outer membrane vesicle (OMV) vaccines are efficacious in humans but have serosubtype-specific serum bactericidal antibody responses directed at the porin protein PorA and the potential for immune selection of PorA-escape mutants.Methods. We prepared an OMV vaccine from a Neisseria meningitidis strain engineered to overexpress genome-derived neisserial antigen ( GNA) 1870, a lipoprotein discovered by genome mining that is being investigated for use in a vaccine.Results. Mice immunized with the modified GNA1870-OMV vaccine developed broader serum bactericidal antibody responses than control mice immunized with a recombinant GNA1870 protein vaccine or an OMV vaccine prepared from wild-type N. meningitidis or a combination of vaccines prepared from wild-type N. meningitidis and recombinant protein. Antiserum from mice immunized with the modified GNA1870-OMV vaccine also elicited greater deposition of human C3 complement on the surface of live N. meningitidis bacteria and greater passive protective activity against meningococcal bacteremia in infant rats. A N. meningitidis mutant with decreased expression of PorA was more susceptible to bactericidal activity of anti-GNA1870 antibodies.Conclusions. The modified GNA1870-OMV vaccine elicits broader protection against meningococcal disease than recombinant GNA1870 protein or conventional OMV vaccines and also has less risk of selection of PorA-escape mutants than a conventional OMV vaccine.