Genetically engineered particulate virus-like structures and their use as vaccine delivery systems.

Abstract

The Orbivirus genus within the family Reoviridae consists of nonenveloped architecturally complex viruses. The icosahedral viruses are 810 A diameter in size and are comprised of two protein shells containing seven proteins (VP1-VP7), surrounding a genome of ten double-stranded RNA segments. The prototype virus, bluetongue virus (BTV), is the etiological agent of a disease that can reach epidemic proportions among sheep and cattle. To develop highly protective virus-like particles, we have developed novel baculovirus multigene expression vector systems which have allowed us to coexpress three, four or five BTV genes from single recombinant vectors. The resultant particulate structures resemble BTV virus-like and subvirus-like particles which are structurally and immunologically indistinguishable from the BTV, and preliminary clinical trials have verified this vaccines safety and efficacy. Unlike live virus vaccines, VLPs are noninfectious and lack virus (or other) DNA/RNA required for replication. VLPs do not replicate in host cells. However, sheep trials have shown that VLPs are more immunogenic than subunit vaccines (viral proteins), or viruses killed by chemical inactivation. In addition, they are effective at eliciting humoral, cell-mediated and mucosal immunities. Virus-like particles (VLPs) are safe to produce and handle. The baculovirus vector and host cells used to make VLPs do not come from mammalian sources (hence they do not contain mammalian-derived pathogens). The multicomponent VLPs have also been utilized as vaccine delivery systems for multiple immunogens including B and T cell epitopes. The expression system described here is a tool which may have a range of applications in industries employing biotechnology to produce vaccines, insecticides, diagnostic and protein reagents.