Institute for Immunization and Prevention, Beijing Center for Disease Prevention and Control, Beijing Research Center for Preventive Medicine, No. 16, Hepingli Middle Street, Dongcheng District, Beijing, 100013, China.
United States Department of Agriculture. Southeast Poultry Research Laboratory, National Poultry Research Center, Agricultural Research Services, 934 College Station Road, Athens, GA, 30605, USA.
Arch Virol. 2021 Dec;166(12):3333-3341. doi: 10.1007/s00705-021-05234-4. Epub 2021 Sep 30.
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.
2014 年西非的埃博拉疫情导致超过 11000 人死亡，凸显了疫苗的需求。一项以人腺病毒 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，用 HAdV-5 疫苗进行同源初免-加强免疫方案会引起强烈的体液免疫反应，但细胞免疫反应较弱。由于存在针对载体的预先存在的免疫，用相同的疫苗进行加强免疫并不能增加细胞免疫反应的幅度，而细胞免疫反应对预防 EBOV 感染有重要贡献。在这里，我们使用反向遗传学技术，基于 LaSota 疫苗株，生成了一种表达埃博拉病毒变体 Makona 的 GP 蛋白的重组新城疫病毒（NDV）（rLS/EB-GP）。使用 ELISA 和 ELISPOT 检测，评估了在同源初免-加强免疫方案或用 HAdV-5 载体疫苗进行异源初免-加强免疫方案中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 进行初免并用 HAdV-5-MakGP 进行加强免疫（NDV+HAdV-5）或相反，用 HAdV-5-MakGP 进行初免并用 rLS/EB-GP 进行加强免疫（HAdV-5+NDV）的小鼠表现出比接受相同疫苗两次更强的 EBOV GP 特异性抗体和细胞免疫反应。在 HAdV-5-MakGP 初免和 rLS/EB-GP 加强免疫（HAdV-5+NDV）的小鼠中检测到最强的 EBOV GP 特异性抗体和 T 细胞反应。这些结果表明，HAdV-5 初免-NDV 加强免疫方案比单独的同源方案更能有效地刺激 EBOV 特异性免疫，表明 NDV 载体在人类疫苗应用中的潜在增强能力。
