Assessment of Hazard Risk Associated with the Intravenous Use of Viral Vectors in Rodents

Viral vectors are emerging as potent basic research tools and gene therapy vehicles in many laboratory animal models. However, little information is available on the potential shedding of these vectors and the consequent exposure risk to investigators and animal care staff from animals over time. This study provides empirical information to Institutional Biosafety Committees and animal care programs, to enhance their ability to perform risk management of laboratory animals treated with viral vectors. Control experiments evaluated the limit of detection of third-generation lentivirus, recombinant adeno-associated virus, and E1-deleted adenovirus tested directly from stocks and after application onto cage plastic or bedding. After inoculation of ICR or NOD-SCID mice, we quantified the recovery of viral vector genomes directly from blood, urine, and fecal samples and assessed the persistence of infectious vector at the site of injection and from soiled bedding at different time points after inoculation. No differences were seen between ICR and NOD-SCID mice. We saw no evidence of vector amplification after in vivo inoculation. The most environmentally persistent vector was recombinant adeno-associated virus, which has no known pathogenicity in humans. In light of these data, we conclude that commonly used replication-deficient viral vectors pose minimal exposure risk by 72 h after inoculation. Prudent precautions at Animal Biosafety Level 2 are warranted during initial administration, but Level 1 safety measures may be sufficient after cage changing and biosafety evaluation.