Structure and Expression in Baculovirus of the Mokola Virus Glycoprotein: An Efficient Recombinant Vaccine

Abstract

The sequence of the glycoprotein gene of the Mokola virus, the more divergent element of the Lyssavirus genus, has been determined and the predicted protein structure compared to its counterpart in rabies vaccine strains. A global similarity of 54.3% was observed. The divergence affects particularly the rabies antigenic sites involved in the B-cell response. This provides a molecular basis for the absence of cross-protection between Mokola and rabies viruses and argues for the necessity of a specific anti-Mokola vaccine. Toward this goal, a cDNA copy of the glycoprotein gene was cloned into the baculovirus and expressed in Spodoptora frugiperda cells. A recombinant protein was produced in substantial amounts at the surface of the insect cells. Although less strongly glycosylated than the native viral glycoprotein produced in BHK-21 cells, the recombinant protein is antigenically and immunologically similar, it is recognized by specific monoclonal antibodies, and protects mice against an intracerebral challenge with Mokola virus. It therefore constitutes the first experimental genetically engineered vaccine against a rabies-related virus, and fulfills the international standard for protection.