首页> 外文期刊>Vaccine >Preclinical immunogenicity and functional activity studies of an A+W meningococcal outer membrane vesicle (OMV) vaccine and comparisons with existing meningococcal conjugate- and polysaccharide vaccines.
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Preclinical immunogenicity and functional activity studies of an A+W meningococcal outer membrane vesicle (OMV) vaccine and comparisons with existing meningococcal conjugate- and polysaccharide vaccines.

机译:A + W脑膜炎球菌外膜囊泡(OMV)疫苗的临床前免疫原性和功能活性研究,以及与现有脑膜炎球菌结合和多糖疫苗的比较。

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Meningococci of serogroups A and W (MenA and MenW) are the main causes of epidemic bacterial meningitis outbreaks in sub-Saharan Africa. In this study we prepared a detergent extracted outer membrane vesicle (dOMV) vaccine from representative African MenA and MenW strains, and compared the immunogenicity of this vaccine with existing meningococcal conjugate and polysaccharide (PS) vaccines in mice. NMRI mice were immunized with preclinical batches of the A+W dOMV vaccine, or with commercially available vaccines; a MenA conjugate vaccine (MenAfriVacReg., Serum Institute of India), ACYW conjugate vaccine (MenveoReg., Novartis) or ACYW PS vaccine (MencevaxReg., GlaxoSmithKline). The mice received 2 doses of 1/10 or 1/50 of a human dose with a three week interval. Immune responses were tested in ELISA, serum bactericidal activity (SBA) and opsonophagocytic activity (OPA) assays. High levels of IgG antibodies against both A and W dOMV were detected in mice receiving the A+W dOMV vaccine. High SBA titers against both MenA and MenW vaccine strains were detected after only one dose of the A+W dOMV vaccine, and the titers were further increased after the second dose. The SBA and OPA titers in mice immunized with dOMV vaccine were significantly higher than in mice immunized with the ACYW-conjugate vaccine or the PS vaccine. Furthermore, the A+W dOMV vaccine was shown to induce SBA and OPA titers against MenA of the same magnitude as the titers induced by the A-conjugate vaccine. In conclusion, the A+W dOMV vaccine induced high levels of functional antibodies to both MenA and MenW strains, levels that were shown to be higher or equal to the levels induced by licensed meningococcal vaccines. Thus, an A+W dOMV vaccine could potentially serve as an alternative or a supplement to existing conjugate and PS vaccines in the African meningitis belt.
机译:A和W血清群(MenA和MenW)的脑膜炎球菌是撒哈拉以南非洲流行的细菌性脑膜炎暴发的主要原因。在这项研究中,我们从代表性的非洲MenA和MenW菌株中制备了去污剂提取的外膜囊泡(dOMV)疫苗,并将该疫苗与现有的脑膜炎球菌结合物和多糖(PS)疫苗在小鼠中的免疫原性进行了比较。用临床前批次的A + W dOMV疫苗或市售疫苗免疫NMRI小鼠; MenA结合疫苗(MenAfriVac Reg。,印度血清研究所),ACYW结合疫苗(Menveo Reg。,诺华)或ACYW PS疫苗(Mencevax Reg。 ,葛兰素史克(GlaxoSmithKline)。小鼠以三周的间隔接受2剂人剂量的1/10或1/50。在ELISA,血清杀菌活性(SBA)和调理吞噬活性(OPA)分析中测试了免疫反应。在接受A + W dOMV疫苗的小鼠中检测到针对A和W dOMV的高水平IgG抗体。仅一剂A + W dOMV疫苗后,就检测到针对MenA和MenW疫苗株的高SBA滴度,第二次接种后滴度进一步提高。用dOMV疫苗免疫的小鼠的SBA和OPA效价显着高于用ACYW结合疫苗或PS疫苗免疫的小鼠。此外,A + W dOMV疫苗可诱导针对MenA的SBA和OPA效价与A偶联疫苗诱导的效价相同。总之,A + W dOMV疫苗诱导了针对MenA和MenW菌株的高水平功能抗体,该水平显示出高于或等于许可的脑膜炎球菌疫苗诱导的水平。因此,A + W dOMV疫苗可能会替代或补充非洲脑膜炎带中现有的结合物和PS疫苗。

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