Analysis of rabies virus pathogenicity and application to the vaccine by using reverse genetics

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Rabies virus deficient in the P gene was generated by reverse genetics from cDNA of HEP-Flury strain lacking the entire P gene. The defective virus was propagated and amplified by rescue of virus, using a cell line that complemented the functions of the deficient gene. The P gene-deficient(def-P) virus replicated its genome and produced progeny viruses in the cell lines that constitutively expressed the P protein, although it grew at a slightly retarded rate compared to the parental strain. In contrast, no progeny virus was produced in the infected host when the def-P virus infected cells that did not express the P protein. The def-P virus was apathogenic in adult and suckling mice, even when inoculated intracranially. Inoculation of def-P virus in mice induced high levels of virus-neutralizing antibody and conferred protective immunity against a lethal rabies infection. These results demonstrate the potential utility of gene-deficient virus as a novel live attenuated rabies vaccine.In an attempt to produce anti-rabies immunoglobulin affordable for people living in developing countries, layer chickens were immunized with a part of the G protein of rabies virus expressed in Escherichia coli. Immunoglobulin (IgY) was purified from the yolks of eggs layed by the immunized hens. It was indicated that the antibody specifically bound to virions as well as cells infected with rabies virus and neutralized rabies virus infisctivity. Moreover, inoculation of the antibody into mice infected with rabies virus reduced the mortality caused by the virus. The IgY directed to the part of the G protein expressed in E.coli could be served as a possible alternative to currently available anti-rabies human or equine immunoglobulin.