UWM categorizes viruses into Risk Groups (RGs) as described by the CDC and NIH in Biosafety in Microbiological and Biomedical Laboratories (BMBL) and the NIH Guidelines. Even if viral vectors are replication-incompetent, determining appropriate containment should always start with an understanding of the inherent risks of the virus used to construct the vector. Tables that outline the appropriate RG for various viruses can be found at the links below:

• NIH Guidelines Appendix B: Classification of Human Etiologic Agents on the Basis of Hazard
• ABSA International Risk Group Database

Different viral vector systems require different levels of containment based on a range of characteristics. After understanding the virus’s Risk Group, a risk assessment should be conducted to determine the appropriate level of containment. In your risk assessment, consider the following:

• Design and generation of the viral vector system: Viral vectors can be designed with a range of safety features that reduce the probability that vectors revert to replication-competent viruses. One of these design factors includes splitting essential virus components across multiple vectors instead of including them all on the same construct. For example, modern adeno-associated virus (AAV) vectors typically split AAV genetic material across three  separate plasmids.
• Method of viral vector production: If you will be propagating your own viral vectors, the method used for viral vector production can significantly impact risk. For example, serial passage of viral vectors in human cell lines can greatly increase the likelihood of reversion to replication competence. Propagating human viral vectors in insect cell lines can be a much safer practice.
• Genes included or targeted: The function of the gene insert included in the viral vector or targeted in the host should be considered during risk assessment. Including or targeting oncogenes, toxin-encoding genes, tumor suppressors, and immunosuppressors typically requires an increase in containment level.
• Shedding from animal models: If viral vectors are used in in vivo animal models, the shedding characteristics of the viral vector need to be considered to determine the appropriate containment at different phases of experimentation. In many cases, animals may be transitioned to housing at a lower biosafety level after a specific amount of time post vector administration when animals are no longer shedding.

ALL work with viral vectors is subject to NIH Guidelines and requires review and approval of a biosafety protocol by the IBC. Protocols are approved for 3-year periods.

• Submit to the IBC online via iManager. Click here to access the submission system and submission instructions. Fill out the form as completely as possible, and provide any additional pertinent information that may assist the committee in assessing risks associated with your work.
• The IBC will determine the final biosafety level appropriate for the work proposed. Research should not begin until IBC approval is granted.

Biosafety and NIH Guidelines trainings are required for all individuals conducting research with viral vectors. If administering viral vectors to animal models, Animal Biosafety training is also required. Find complete biosafety training requirements on the Biosafety Training webpage.