Abstract
There are currently no licensed therapeutic treatment or preventive vaccines against Ebolavirus disease, and the 2013–2016 West African outbreak of Ebolavirus disease spread rapidly and resulted in almost 30,000 cases and more than 11,000 deaths. However, the devastating outbreak has spurred the development of novel Ebolavirus vaccines. Here, we demonstrate that alphavirus-based DNA-launched self-replicating RNA replicon vaccines (DREP) encoding either the glycoprotein (GP) gene or co-expressing the GP and VP40 genes of Sudan or Zaire Ebolavirus are immunogenic in mice inducing both binding and neutralizing antibodies as well as CD8 T cell responses. In addition, antibodies were cross-reactive against another Ebolavirus, although the specificity was higher for the vaccination antigen. DREP vaccines were more immunogenic than recombinant MVA vaccines expressing the same Ebolavirus antigens. However, a DREP prime followed by an MVA boost immunization regimen improved vaccine immunogenicity as compared to DREP and MVA homologous prime-boost immunizations. Moreover, we show that a bivalent approach targeting both Sudan and Zaire Ebolavirus can be employed without significant loss of immunity. This opens for further investigation of a pan-Ebolavirus or even a pan-filovirus vaccine.
Highlights
Ebolavirus, the causative agent of Ebolavirus Disease (EVD), was discovered in 1976 during outbreaks in Zaire and Sudan[1]
We describe the immunogenicity of DNA-launched replicons (DREP) vaccines encoding the GP and GP-VP40 genes from SUDV and EBOV Ebolavirus species in different prime-boost immunization regimens
We hypothesized that DREP Ebolavirus constructs expressing either GP or GP plus VP40 may differ in their immunogenic properties
Summary
Ebolavirus, the causative agent of Ebolavirus Disease (EVD), was discovered in 1976 during outbreaks in Zaire and Sudan[1]. Despite the considerable advances towards a licensed Ebolavirus vaccine, it is yet unknown whether any of the present candidates will meet all the desirable requirements for a vaccine against Ebola such as being safe with broad and durable immunity Both the VSV and adenovirus vectors have passed safety testing in clinical trials, there are still some concerns that rare events are unnoticed in clinical trials with limited numbers of volunteers. The encoded replicase will amplify the replicon in the cytoplasm as well as transcribe an mRNA encoding the Ebolavirus antigen from an internal viral promoter in the replicon Such DREP Ebolavirus vaccines offer several advantages; they can be and rapidly constructed using synthetic cDNA in response to an emerging threat, and production times are short. We describe the immunogenicity of DREP vaccines encoding the GP and GP-VP40 genes from SUDV and EBOV Ebolavirus species in different prime-boost immunization regimens
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