Inactivation of adenovirus and simian virus 40 tumorigenicity in hamsters by vaccine processing methods.
The effectiveness of the adenovirus vaccine inactivation process in destroying the tumorigenic potential for hamsters of adenoviruses, simian virus 40 (SV-40), and adenovirus-SV-40 hybrids was studied. Baby hamsters injected with untreated virus and with samples subjected to the complete inactivation process and to portions of the process were observed for tumor development for periods in excess of 300 days. Over 20,000 hamsters were injected. From 1 to 7 hr of exposure to formaldehyde at a concentration of 0.031 m at 37 C was sufficient to destroy the tumorigenicity observed in the nontreated preparations. Since the inactivation process included 48 hr of exposure at 37 C to 0.031 m formaldehyde plus treatment with ultraviolet (UV) and with beta-propiolactone (BPL), it was concluded that the process has a large margin of safety. Adenovirus isolates free from tumorigenic potential are difficult, if not impossible, to obtain. Therefore, a proven inactivation process appears to provide the best assurance for obtaining adenovirus vaccines free from such potential. Data presented suggest that the tumorigenic property of the viruses studied might be independent of the infectivity of the preparation. The tumorigenic property was found to be highly susceptible to formaldehyde, but less sensitive to BPL or UV treatment. In contrast, treatment with UV or BPL decreased viral infectivity more readily than tumorigenicity. The three-stage inactivation process (formaldehyde, UV, and BPL) inactivated both tumorigenicity and infectivity.
D000256:Adenoviridae / Q000528:radiation effects; D000818:Animals; D006224:Cricetinae; D005557:Formaldehyde / Q000494:pharmacology*; D006824:Hybridization, Genetic; D007783:Lactones / Q000494:pharmacology; D009374:Neoplasms, Experimental; D009858:Oncogenic Viruses / Q000187:drug effects*; D013539:Simian virus 40 / Q000528:radiation effects; D014466:Ultraviolet Rays; D014765:Viral Vaccines
D007783:Lactones; D014765:Viral Vaccines; D005557:Formaldehyde