The development of multiagent
vaccines offers the advantage of eliciting protection against multiple diseases with minimal inoculations over a shorter time span. We report here the results of using formulations of individual
Venezuelan equine encephalitis (VEE) virus replicon-vectored
vaccines against a
bacterial disease,
anthrax; a
viral disease, Marburg
fever; and against a toxin-mediated disease,
botulism. The individual VEE replicon particles (VRP) expressed mature 83-kDa protective
antigen (MAT-PA) from Bacillus anthracis, the
glycoprotein (GP) from Marburg virus (MBGV), or the H(C) fragment from
botulinum neurotoxin (BoNT H(C)). CBA/J mice inoculated with a mixture of VRP expressing BoNT H(C) serotype C (BoNT/C H(C)) and MAT-PA were 80% protected from a B. anthracis (Sterne strain) challenge and then 100% protected from a sequential BoNT/C challenge. Swiss mice inoculated with individual VRP or with mixtures of VRP
vaccines expressing BoNT H(C) serotype A (
BoNT/A H(C)), MAT-PA, and MBGV-GP produced antibody responses specific to the corresponding replicon-expressed
protein. Combination of the different VRP
vaccines did not diminish the antibody responses measured for Swiss mice inoculated with formulations of two or three VRP
vaccines as compared to mice that received only one VRP
vaccine. Swiss mice inoculated with VRP expressing
BoNT/A H(C) alone or in combination with VRP expressing MAT-PA and MBGV GP, were completely protected from a
BoNT/A challenge. These studies demonstrate the utility of combining individual VRP
vaccines into multiagent formulations for eliciting protective immune responses to various types of diseases.