Development and preclinical evaluation of an alphavirus replicon particle vaccine for cytomegalovirus.
We used a replication-incompetent, single-cycle, alphavirus replicon vector system to produce virus-like replicon particles (VRP) expressing the extracellular domain of human cytomegalovirus (CMV) glycoprotein B or a pp65/IE1 fusion protein. Efficient production methods were scaled to produce pilot lots and clinical lots of each alphavirus replicon vaccine component. The vaccine induced high-titered antibody responses in mice and rabbits, as measured by ELISA and CMV neutralization assays, and robust T-cell responses in mice, as measured by IFN-gamma ELISPOT assay. A toxicity study in rabbits showed no adverse effects in any toxicology parameter. These studies support clinical testing of this novel CMV alphavirus replicon vaccine in humans.
Reap, EA; Morris, J; Dryga, SA; Maughan, M; Talarico, T; Esch, RE; Negri, S; Burnett, B; Graham, A; Olmsted, RA; Chulay, JD
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