Mutant Native Outer Membrane Vesicles Combined with a Serogroup A Polysaccharide Conjugate Vaccine for Prevention of Meningococcal Epidemics in Africa.
Mutant Native Outer Membrane Vesicles Combined with a Serogroup A Polysaccharide Conjugate Vaccine for Prevention of Meningococcal Epidemics in Africa.
复制标题
DOI：
10.1371/journal.pone.0066536
复制
发表时间：
2013
期刊：
影响因子：
3.7
通讯作者：
Granoff DM
中科院分区：
文献类型：
--
作者：
Pajon R;Fergus AM;Granoff DM
在撒哈拉以南非洲使用的脑膜炎球菌血清群A（MenA）多糖结合疫苗不能预防MenW或MenX菌株引起的疾病，这些菌株也会在该地区引起流行病。我们研究了具有过表达因子H结合蛋白（NOMV-fHbp）的天然外膜囊泡的疫苗潜力，该囊泡靶向非洲脑膜炎球菌菌株中的抗原，并与MenA多糖缀合物疫苗相结合。NOMV-fHbp疫苗是从具有PorA P1.5，2、减毒内毒素（Δ LpxL 1）、缺失的荚膜基因和变体组1中过表达的fHbp的突变型非洲MenW毒株制备的。用Al（OH）3吸附NOMV-fHbp并用于重构冻干的MenA缀合物疫苗，其通常用脑膜炎球菌四价缀合物疫苗（MCV 4-CRM，Novartis）中的液体MenC、Y和W缀合物重构。用NOMV-fHbp疫苗单独免疫的小鼠产生了针对15种测试的非洲MenA菌株中的13种的血清杀菌（人补体）活性; 10种非洲MenX菌株中的10种，7种非洲MenW菌株中的7种，以及具有fHbp变体组1的6种遗传多样性MenB菌株中的6种（包括来自冈比亚的1种菌株）。组合NOMV-fHbp/MenA缀合物疫苗引发针对所测试的两种MenA菌株的高血清杀菌效价，所述MenA菌株对由单独的NOMV-fHbp引发的杀菌抗体具有抗性;所述组合引发针对MenA和MenW菌株的效价高于由对照MCV 4-CRM疫苗引发的效价（P<0.05）;以及针对MenX和MenB菌株的高效价。对于大多数菌株，由对照NOMV-fHbp敲除疫苗引起的滴度<1∶10，除了当菌株PorA与疫苗匹配时（滴度>1∶000）。NOMV-fHbp/MenA结合疫苗提供了与四价脑膜炎球菌结合疫苗相似或更高的针对MenA和MenW菌株的覆盖率，并延长了针对造成非洲流行病的MenX菌株和在变异组1中具有fHbp的MenB菌株的保护。
The meningococcal serogroup A (MenA) polysaccharide conjugate vaccine used in Sub-Saharan Africa does not prevent disease caused by MenW or MenX strains, which also cause epidemics in the region. We investigated the vaccine-potential of native outer membrane vesicles with over-expressed factor H-binding protein (NOMV-fHbp), which targeted antigens in African meningococcal strains, and was combined with a MenA polysaccharide conjugate vaccine. The NOMV-fHbp vaccine was prepared from a mutant African MenW strain with PorA P1.5,2, attenuated endotoxin (ΔLpxL1), deleted capsular genes, and over-expressed fHbp in variant group 1. The NOMV-fHbp was adsorbed with Al(OH)3 and used to reconstitute a lyophilized MenA conjugate vaccine, which normally is reconstituted with liquid MenC, Y and W conjugates in a meningococcal quadrivalent conjugate vaccine (MCV4-CRM, Novartis). Mice immunized with the NOMV-fHbp vaccine alone developed serum bactericidal (human complement) activity against 13 of 15 African MenA strains tested; 10 of 10 African MenX strains, 7 of 7 African MenW strains, and 6 of 6 genetically diverse MenB strains with fHbp variant group 1 (including 1 strain from The Gambia). The combination NOMV-fHbp/MenA conjugate vaccine elicited high serum bactericidal titers against the two MenA strains tested that were resistant to bactericidal antibodies elicited by the NOMV-fHbp alone; the combination elicited higher titers against the MenA and MenW strains than those elicited by a control MCV4-CRM vaccine (P<0.05); and high titers against MenX and MenB strains. For most strains, the titers elicited by a control NOMV-fHbp knock out vaccine were <1∶10 except when the strain PorA matched the vaccine (titers >1∶000). The NOMV-fHbp/MenA conjugate vaccine provided similar or higher coverage against MenA and MenW strains than a quadrivalent meningococcal conjugate vaccine, and extended protection against MenX strains responsible for epidemics in Africa, and MenB strains with fHbp in variant group 1.
登录
查看更多内容
影响因子：
5.5
作者：
Brunelli, Brunella;Del Tordello, Elena;Serruto, Davide
通讯作者：
Serruto, Davide
影响因子：
--
作者：
Chiavolini, Damiana;Weir, Susan;Wetzler, Lee M.
通讯作者：
Wetzler, Lee M.
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：
7.7
作者：
Galloway, Yvonne;Stehr-Green, Paul;O'Hallahan, Jane
通讯作者：
O'Hallahan, Jane
影响因子：
3.7
作者：
Caugant, Dominique A.;Kristiansen, Paul A.;Bonte, Laurence
通讯作者：
Bonte, Laurence