Studies on pathogenic, immunogenic, and protective efficiency of fox rabies virus before and after adaptation to cell culture: application to vaccination against rabies.
Rabies virus from the submandibular salivary gland of a naturally infected fox was adapted to growth in BHK-21 cells. The pathogenicity of the original isolate and the cell culture adapted virus were compared by the intramuscular and oral routes in mice and foxes. Animals surviving exposure were tested for serum rabies antibodies (immunogenic efficiency) and for their ability to survive a second challenge with rabies virus (protective efficiency). In mice, ratios between lethal and protective doses of the two strains via the oral or muscular route were similar. In foxes, however, pathogenic efficiency was modified after cell culture adaptation, although good immunogenic and protective efficiency was maintained. Inoculation via the oral route resulted in lethal infection with the wild-type strain and survival (with some subsequent immunity) with the cell-adapted strain. Via the intramuscular route, foxes given high doses of cell culture adapted virus survived whereas several foxes given lower doses died and virus could not be reisolated. It is concluded that safety testing of modified strains should be done with different dilutions of virus in the target species. "Autosterilizing" infections may result in erroneous diagnosis.