Bactericidal antibody responses elicited by a meningococcal outer membrane vesicle vaccine with overexpressed factor H-binding protein and genetically attenuated endotoxin.
Bactericidal antibody responses elicited by a meningococcal outer membrane vesicle vaccine with overexpressed factor H-binding protein and genetically attenuated endotoxin.
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DOI：
10.1086/589308
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发表时间：
2008-07-15
期刊：
影响因子：
--
通讯作者：
Granoff DM
中科院分区：
文献类型：
--
作者：
Koeberling O;Seubert A;Granoff DM
外膜囊泡（OMV）疫苗从突变N。脑膜炎病毒株工程改造过表达因子H结合蛋白（fHbp）引起广泛的保护性血清抗体反应的小鼠。所研究的疫苗未用去污剂处理以避免提取fHbp，其是一种脂蛋白。由于它们的高内毒素含量，疫苗对人类施用是不安全的。我们制备了一种天然的OMV疫苗，从工程菌株过表达fHbp，其中编码LpxL1的基因被灭活，据报道，这降低了内毒素活性。来自突变体的OMV疫苗通过人外周血单核细胞诱导促炎细胞因子的能力与去污剂提取的野生型OMV相似或更低，并且活性比天然野生型OMV低1000至10，000倍。在小鼠中，来自突变体的OMV疫苗引起针对一组异源N.与对照多组分重组蛋白疫苗或去污剂提取的OMV疫苗相比，本发明的疫苗对脑膜炎球菌菌株的保护作用更强，所述去污剂提取的OMV疫苗先前已被证明在人类中赋予针对脑膜炎球菌疾病的保护作用。这些数据说明了开发具有广泛免疫原性的天然OMV疫苗的潜力，该疫苗具有降低的内毒素活性，可能适用于人体试验。
Outer membrane vesicle (OMV) vaccines from mutant N. meningitidis strains engineered to over-express factor H-binding protein (fHbp) elicited broadly protective serum antibody responses in mice. The vaccines investigated were not treated with detergents to avoid extracting fHbp, which is a lipoprotein. Because of their high endotoxin content, the vaccines would not be safe to administer to humans. We prepared a native OMV vaccine from a strain engineered to over-express fHbp and in which the gene encoding LpxL1 was inactivated, which reportedly decreased endotoxin activity. The OMV vaccine from the mutant had similar or lower ability to induce proinflammatory cytokines by human peripheral blood mononuclear cells as a detergent-extracted wildtype OMV, and 1000- to 10,000-fold lower activity than a native wildtype OMV. In mice, the OMV vaccine from the mutant elicited higher serum bactericidal antibody responses against a panel of heterologous N. meningitidis strains than a control multicomponent recombinant protein vaccine, or a detergent-extracted OMV vaccine that previously had been demonstrated to confer protection against meningococcal disease in humans. The data illustrate the potential to develop a broadly immunogenic native OMV vaccine with decreased endotoxin activity that is potentially suitable for testing in humans.
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影响因子：
5.5
作者：
Claassen, I;Meylis, J;Poolman, J
通讯作者：
Poolman, J
DOI：
10.1084/jem.20021911
发表时间：
2003-03-17
期刊：
The Journal of experimental medicine
影响因子：
--
作者：
Masignani V;Comanducci M;Giuliani MM;Bambini S;Adu-Bobie J;Arico B;Brunelli B;Pieri A;Santini L;Savino S;Serruto D;Litt D;Kroll S;Welsch JA;Granoff DM;Rappuoli R;Pizza M
通讯作者：
Pizza M
纳达（Nada），奈瑟氏菌脑膜炎的新型疫苗候选者。
影响因子：
15.3
作者：
Comanducci, Maurizio;Bambini, Stefania;Brunelli, Brunella;Adu-Bobie, Jeannette;Arico, Beatrice;Capecchi, Barbara;Giuliani, Marzia Monica;Masignani, Vega;Santini, Laura;Savino, Silvana;Granoff, Dan M;Caugant, Dominique A;Pizza, Mariagrazia;Rappuoli, Rino;Mora, Marirosa
通讯作者：
Mora, Marirosa
DOI：
10.1073/pnas.0603940103
发表时间：
2006-07-18
影响因子：
11.1
作者：
Giuliani, Marzia M.;Adu-Bobie, Jeannette;Pizza, Mariagrazia
通讯作者：
Pizza, Mariagrazia
影响因子：
6.4
作者：
Hou, VC;Koeberling, O;Granoff, DM
通讯作者：
Granoff, DM