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

• Published in: Virology (New York, N.Y.) Vol. 194; no. 1; pp. 59 - 69
• Main Authors: Tordo, Noël, Bourhy, Hervé, Sather, Susan, Ollo, Roger
• Format: Journal Article
• Language: English
• Published: San Diego, CA Elsevier Inc 01.05.1993; Elsevier
• Subjects: Amino Acid Sequence; Animals; Baculoviridae - genetics; baculovirus; Base Sequence; Biological and medical sciences; Cats; Cells, Cultured; Cloning, Molecular; Cricetinae; Fundamental and applied biological sciences. Psychology; Genes, Viral - genetics; Mice; Microbiology; Mokola virus; Molecular Sequence Data; Moths - cytology; Rabies virus - genetics; Rabies virus - immunology; Recombinant Proteins - biosynthesis; Recombinant Proteins - immunology; Rhabdoviridae - genetics; Rhabdoviridae - immunology; Sequence Homology, Amino Acid; Spodoptera frugiperda; Vaccines, antisera, therapeutical immunoglobulins and monoclonal antibodies; Vaccines, Synthetic - immunology; Viral Structural Proteins - genetics; Viral Vaccines - biosynthesis; Viral Vaccines - genetics; Viral Vaccines - immunology; Virology; Virus Diseases - immunology; Virus Diseases - prevention & control; Immunoprotection; Nucleotide sequence; Mokola virus; Insecta; Sequence alignment; Spodoptera frugiperda; Homology; Glycoproteins; Vaccine; Gene expression; Virus; Antigenicity; Gene; Immunogenicity; Rhabdoviridae; Arthropoda; Lepidoptera; Lyssavirus; Noctuidae; Recombinant protein; Invertebrata; Molecular cloning; Comparative study; Aminoacid sequence
• ISSN: 0042-6822; 1096-0341
• DOI: 10.1006/viro.1993.1235

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.