Contamination of live attenuated vaccines with an infectious feline endogenous retrovirus (RD-114 virus)
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Retroviruses are classified as exogenous and endogenous retroviruses according to the mode of transmission. Endogenous retroviruses (ERVs) are retroviruses which have been integrated into germ-line cells and inherited from parents to offspring. Most ERVs are inactivated by deletions and mutations; however, certain ERVs maintain their infectivity and infect the same host and new hosts as exogenous retroviruses. All domestic cats have infectious ERVs, termed RD-114 virus. Several canine and feline attenuated vaccines are manufactured using RD-114 virus-producing cell lines such as Crandell-Rees feline kidney cells; therefore, it is possible that infectious RD-114 virus contaminates live attenuated vaccines. Recently, Japanese and UK research groups found that several feline and canine vaccines were indeed contaminated with infectious RD-114 virus. This was the first incidence of contamination of ‘infectious’ ERVs in live attenuated vaccines. RD-114 virus replicates efficiently in canine cell lines and primary cells. Therefore, it is possible that RD-114 virus infects dogs following inoculation with contaminated vaccines and induces proliferative diseases and immune suppression, if it adapts to grow efficiently in dogs. In this review, we summarize the incidence of contamination of RD-114 virus in live attenuated vaccines and potential risks of infection with RD-114 virus in dogs.
KeywordsYellow Fever Vaccine Reverse Transcriptase Assay CRFK Cell Canine Cell Line Spleen Necrosis Virus
We thank Peter Gee (Kyoto University) for his generous help in the preparation of this manuscript. This work was supported by grants from the Japan Society for the Promotion of Science and from the Bio-Oriented Technology Research Advancement Institution in Japan, and by contributions from Kyoritsu Seiyaku Corporation (Chiyoda-ku, Tokyo, Japan), Merial Japan (Chiyoda-ku, Tokyo, Japan), and Nisseiken Co. Ltd. (Ome, Tokyo, Japan).
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