We evaluated the immunogenicity of virus-like replicon particles (VRP) derived from an attenuated strain of
the alphavirus Venezuelan equine encephalitis virus, encoding two pre-erythrocytic Plasmodium yoelii antigens, in mice.
Three immunizing doses were superior to two, and the subcutaneous route was comparable to intramuscular and more
immunogenic than intradermal, at doses between 5x105-5x108 IU. VRP vaccines were capable of overcoming the traditionally
low immunogenicity of the PyHEP17 antigen when delivered as a DNA vaccine, particularly evident with regard
to enhancing specific IgG responses. Furthermore, a heterologous VRP prime and poxvirus boost regimen induced a significant
enhancement of IFN-γ responses as compared with homologous VRP or DNA immunization, which was equal or
greater to that induced by DNA prime followed by poxvirus boost. These data demonstrate the potential of VRP as a vaccine
delivery system to enhance protective immune responses to malaria.