Department of Veterinary Medicine, University of Cambridge, Cambridge, United Kingdom.
Front Immunol. 2024 Sep 24;15:1473064. doi: 10.3389/fimmu.2024.1473064. eCollection 2024.
More affordable and effective vaccines against bacterial meningitis caused by serogroup B are still required for global prevention. We have previously shown that modified outer membrane vesicles (mOMVs) from commensal can be used as a platform to induce immune responses against meningococcal antigens. The aim of the present study was to use a combination of two genetically engineered mOMVs to express multiple antigens from known to be involved in protective immunity to meningococcal meningitis (different variants of factor H binding protein (fHbp), Heparin Binding Antigen (NHBA) and Adhesin A (NadA)). Antigen expression in the mOMVs was confirmed by Western blotting; detoxification of the lipooligosaccharide (LOS) was confirmed by measuring human Toll-like receptor 4 (hTLR4) activation using cell assays. Mice immunised with a combination of two mOMVs expressing fHbp, NHBA and NadA produced antibodies to all the antigens. Furthermore, serum bactericidal activity (SBA) was induced by the immunisation, with mOMVs expressing NadA displaying high SBA titres against a MenB strain. The work highlights the potential of mOMVs from to induce functional immune responses against multiple antigens involved in the protective immune response to meningococcal disease.
仍然需要更经济实惠且有效的 B 群脑膜炎球菌疫苗来进行全球预防。我们之前已经表明，共生菌的修饰外膜囊泡（mOMVs）可用作诱导针对脑膜炎奈瑟菌抗原的免疫反应的平台。本研究的目的是使用两种基因工程化的 mOMVs 组合来表达已知参与对脑膜炎奈瑟菌脑膜炎的保护性免疫的多种抗原（来自 fHbp 的不同变体、肝素结合抗原（NHBA）和粘附素 A（NadA））。通过 Western blot 确认 mOMVs 中的抗原表达；通过使用细胞测定法测量人 Toll 样受体 4（hTLR4）的激活来确认脂寡糖（LOS）的解毒。用表达 fHbp、NHBA 和 NadA 的两种 mOMVs 组合免疫的小鼠产生针对所有抗原的抗体。此外，免疫接种诱导了血清杀菌活性（SBA），表达 NadA 的 mOMVs 对 MenB 菌株显示出高 SBA 效价。这项工作强调了来自 的 mOMVs 诱导针对参与脑膜炎奈瑟菌疾病保护性免疫的多种抗原的功能性免疫反应的潜力。
