Recombinant RNA replicons derived from attenuated Venezuelan equine encephalitis virus protect guinea pigs and mice from Ebola hemorrhagic fever virus

RNA replicons derived from an attenuated strain of Venezuelan equine enceph alitis virus (VEE), an alphavirus, were configured as candidate vaccines fo r Ebola hemorrhagic fever. The Ebola nucleoprotein (NP) or glycoprotein (GP ) genes were introduced into the VEE RNA downstream from the VEE 26S promot er in place of the VEE structural protein genes. The resulting recombinant replicons, expressing the NP or GP genes, were packaged into VEE replicon p articles(NP-VRP and GP-VRP, respectively) using a bipartite helper system t hat provided the VEE structural proteins in trans and prevented the regener ation of replication-competent VEE during packaging. The immunogenicity of NP-VRP and GP-VRP and their ability to protect against lethal Ebola infecti on were evaluated in BALB/c mice and in two strains of guinea pigs. The GP- VRP alone, or in combination with NP-VRP, protected both strains of guinea pigs and BALB/c mice, while immunization with NP-VRP alone protected BALB/c mice, but neither strain of guinea pig. Passive transfer of sera from VRP- immunized animals did not confer protection against lethal challenge. Howev er, the complete protection achieved with active immunization with VRP, as well as the unique characteristics of the VEE replicon vector, warrant furt her testing of the safety and efficacy of NP-VRP and GP-VRP in primates as candidate vaccines against Ebola hemorrhagic fever. Published by Elsevier S cience Ltd.