Potentiation of anthrax vaccines using protective antigen-expressing viral replicon vectors

• SFV replicon PA or PA4-DNA vaccines elicit stronger immunity than non-viral DNA ones.
• SFV VRP-PA/SPA vaccines induce robust humoral response and protection against anthrax.
• PA-expressing vaccines afford better protection against anthrax than the PA4 ones.
• PA-expressing SFV replicon vaccines afford completely protection against anthrax.
• PA-expressing SFV replicon vaccines may be suitable as candidate vaccines of anthrax.

DNA vaccines require improvement for human use because they are generally weak stimulators of the immune system in humans. The efficacy of DNA vaccines can be improved using a viral replicon as vector to administer antigen of pathogen. In this study, we comprehensively evaluated the conventional non-viral DNA, viral replicon DNA or viral replicon particles (VRP) vaccines encoding different forms of anthrax protective antigen (PA) for specific immunity and protective potency against anthrax. Our current results clearly suggested that these viral replicon DNA or VRP vaccines derived from Semliki Forest virus (SFV) induced stronger PA-specific immune responses than the conventional non-viral DNA vaccines when encoding the same antigen forms, which resulted in potent protection against challenge with the Bacillus anthracis strain A16R. Additionally, the naked PA-expressing SFV replicon DNA or VRP vaccines without the need for high doses or demanding particular delivery regimens elicited robust immune responses and afforded completely protective potencies, which indicated the potential of the SFV replicon as vector of anthrax vaccines for use in clinical application. Therefore, our results suggest that these PA-expressing SFV replicon DNA or VRP vaccines may be suitable as candidate vaccines against anthrax.