Study on development of a live attenuated vaccine for equine influenza infection using reverse genetics

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Equine influenza is an important contagious respiratory disease of horses. In the field of veterinary medicine, equine influenza is recognized as a serious problem because it causes economical loss. Inactivated vaccine for equine influenza has been used to control infection; however its efficacy is not satisfactory.The aim of this study is to develop a live attenuated vaccine for equine influenza infection. A live attenuated vaccine for influenza virus can be generated by insertion of a gene encoding target protein into genome of an attenuated virus. To this end we established a strategy to generate recombinant influenza virus that contained a foreign gene using reverse genetics.The results we obtained were as follows.1.Regions in the genome RNA segments required for their efficient incorporation into virus particle were found. The regions were located at the both ends of each genome segments and contained the protein encoding sequences. Thus we identified packaging signals in the genome segments of influenza A virus.2.Identification of the packaging signals allowed us to produce a recombinant virus with a gene encoding foreign protein. By fusion of the packaging signals to the foreign genes, influenza A virus with the gene encoding the green fluorescent protein, the hemagglutinin and/or neuraminidase of influenza B virus or the glycoprotein of vesicular stomatitis virus was successfully generated.3.Infection of the influenza A virus with the gene encoding influenza B virus glycoprotein induced immune response in mice.So far, knowledge of mutations that lead to attenuation of influenza A virus has been accumulated. Therefore introduction of attenuation mutations and the system to generate recombinant influenza A virus enable us to establish a live attenuated vaccine not only for equine influenza but also other infections.