The 2014 Ebola outbreak in West Africa resulted in more than 11,000 deaths, highlighting the need for a vaccine. A phase I clinical trial of a human adenovirus type 5 vector-based Ebola virus (EBOV) vaccine (HAdV-5-MakGP) showed that a homologous prime-boost regimen with HAdV-5 vaccine elicited a robust humoral response but a weak cellular immune response. Due to pre-existing anti-vector immunity, boosting with the same vaccine did not increase the magnitude of the cellular immune response, which contributes significantly to protection against EBOV infection. Here, we generated a recombinant Newcastle disease virus (NDV), based on the LaSota vaccine strain, expressing the GP protein of the EBOV variant Makona (rLS/EB-GP) using reverse genetics technology. The humoral and cellular immune responses to this vaccine candidate in mice immunized using a homologous prime-boost regimen or a heterologous prime-boost regimen with the HAdV-5-vectored Ebola vaccine were assessed using ELISA and ELISPOT assays. The ELISA and ELISPOT results showed that mice primed with rLS/EB-GP and boosted with HAdV-5-MakGP (NDV+HAdV-5) or, reversed, primed with HAdV-5-MakGP and boosted with rLS/EB-GP (HAdV-5+NDV) exhibited more-potent EBOV GP-specific antibody and cellular immune responses than those receiving the same vaccine twice. The most robust EBOV GP-specific antibody and T-cell responses were detected in the HAdV-5-MakGP-primed and rLS/EB-GP-boosted (HAdV-5+NDV) mice. These results suggest that the HAdV-5 prime-NDV boost regimen is more effective in stimulating EBOV-specific immunity than homologous regimens alone, indicating the potential boosting ability of the NDV vector in human vaccine use.

中文翻译：

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HAdV-5 和 NDV 载体的异源初免加强方案比小鼠中的同源方案对埃博拉病毒产生更强的免疫反应。

2014 年在西非爆发的埃博拉病毒导致 11,000 多人死亡，凸显了对疫苗的需求。以人类腺病毒 5 型载体为基础的埃博拉病毒 (EBOV) 疫苗 (HAdV-5-MakGP) 的 I 期临床试验表明，采用 HAdV-5 疫苗的同源初免增强方案引起了强烈的体液反应，但细胞免疫功能较弱回复。由于预先存在抗载体免疫，用相同的疫苗加强免疫不会增加细胞免疫反应的幅度，这对防止 EBOV 感染有显着贡献。在这里，我们生成了一种基于 LaSota 疫苗株的重组新城疫病毒 (NDV)，使用反向遗传学技术表达 EBOV 变体 Makona (rLS/EB-GP) 的 GP 蛋白。使用 ELISA 和 ELISPOT 测定法评估了使用同源初免-加强方案或异源初免-加强方案与 HAdV-5 载体埃博拉疫苗免疫的小鼠对该候选疫苗的体液和细胞免疫反应。ELISA 和 ELISPOT 结果表明，用 rLS/EB-GP 引发并用 HAdV-5-MakGP (NDV+HAdV-5) 加强的小鼠，或者相反，用 HAdV-5-MakGP 和 rLS/EB-GP 加强的小鼠（ HAdV-5+NDV) 表现出比接受相同疫苗两次的人更有效的 EBOV GP 特异性抗体和细胞免疫反应。在 HAdV-5-MakGP-primed 和 rLS/EB-GP-boosted (HAdV-5+NDV) 小鼠中检测到最强大的 EBOV GP 特异性抗体和 T 细胞反应。这些结果表明，HAdV-5 初免-NDV 加强方案在刺激 EBOV 特异性免疫方面比单独使用同源方案更有效，