Vaccine Research Center, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD, United States.
Front Immunol. 2021 Mar 9;12:627688. doi: 10.3389/fimmu.2021.627688. eCollection 2021.
Heterologous prime-boost immunization regimens are a common strategy for many vaccines. DNA prime rAd5-GP boost immunization has been demonstrated to protect non-human primates against a lethal challenge of Ebola virus, a pathogen that causes fatal hemorrhagic disease in humans. This protection correlates with antibody responses and is also associated with IFNγ TNFα double positive CD8 T-cells. In this study, we compared single DNA vs. multiple DNA prime immunizations, and short vs. long time intervals between the DNA prime and the rAd5 boost to evaluate the impact of these different prime-boost strategies on vaccine-induced humoral and cellular responses in non-human primates. We demonstrated that DNA/rAd5 prime-boost strategies can be tailored to induce either CD4 T-cell or CD8 T-cell dominant responses while maintaining a high magnitude antibody response. Additionally, a single DNA prime immunization generated a stable memory response that could be boosted by rAd5 3 years later. These results suggest DNA/rAd5 prime-boost provides a flexible platform that can be fine-tuned to generate desirable T-cell memory responses.
异源初免-加强免疫方案是许多疫苗的常用策略。DNA 初免 rAd5-GP 加强免疫已被证明可保护非人类灵长类动物免受致命性埃博拉病毒的攻击，这种病原体可导致人类致命性出血热。这种保护与抗体反应相关，也与 IFNγ TNFα 双阳性 CD8 T 细胞相关。在这项研究中，我们比较了单次 DNA 与多次 DNA 初免免疫，以及 DNA 初免与 rAd5 加强免疫之间的短时间和长时间间隔，以评估这些不同的初免-加强策略对非人类灵长类动物疫苗诱导的体液和细胞反应的影响。我们证明，DNA/rAd5 初免-加强策略可以根据需要诱导 CD4 T 细胞或 CD8 T 细胞优势反应，同时保持高抗体反应。此外，单次 DNA 初免免疫可产生稳定的记忆反应，可在 3 年后由 rAd5 加强。这些结果表明，DNA/rAd5 初免-加强提供了一个灵活的平台，可以进行微调以产生理想的 T 细胞记忆反应。
