Ebola-GP DNA Prime rAd5-GP Boost: Influence of Prime Frequency and Prime/Boost Time Interval on the Immune Response in Non-human Primates

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 IFN gamma(+) TNF alpha(+) 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.

Automated summary

Heterologous prime-boost immunization regimens have been shown to protect non-human primates against Ebola virus, with different strategies inducing either CD4(+) or CD8(+) T-cell responses while maintaining high levels of antibodies. A single DNA prime immunization can generate a stable memory response that can be boosted 3 years later by rAd5. This suggests that DNA/rAd5 prime-boost provides a flexible platform for generating desirable T-cell memory responses.