Genetically engineered multi‐component virus‐like particles as veterinary vaccines

Abstract

Multiprotein structures can be constructed to mimic virus particles. These engineered particles lack genetic material and are not infectious but they can elicit protective immune responses in animals against challenges with infectious viruses. As a prototype, insect cells were co-infected with two recombinant baculoviruses. One recombinant baculovirus contained an insert of L2 and M5 genes, which encode for outer capsid proteins VP2 and VP5, respectively, from bluetongue virus (BTV) downstream of duplicated copies of the baculovirus (Autographa californica nuclear polyhedrosis virus, AcNPV) polyhedrin promoter. Another recombinant baculovirus expressed two major core proteins (VP3 and VP7) from BTV virions. The co-infected cells synthesized non-infectious, double-shelled, virus-like particles (VLP). The VLP resembled the authentic BTV in size, appearance, and biochemical constitution but they lacked the double-stranded-RNA genome and three minor polypeptides normally contained in the icosahedral inner capsid. The VLP consisted of an outer shell of VP2 and VP5 from US BTV-10 attached to an icosahedral framework formed by the two major core proteins VP3 and BTV-17 and VP7 from US BTV-10. Sheep immunized with VLP expressing BTV capsid proteins produced antibodies that neutralized homologous serotypes of BTV. The assembly of VLP from different proteins simultaneously expressed indicates the potential of this novel approach for producing safe and effective vaccines against several viral agents.