What safety considerations need to be taken when producing viral vectors?

Most viruses used as vectors do not express the genes which cause cytotoxicity. However, even non-virulent viruses still have the potential to elicit pyrogenic and immunogenic responses – which can be serious or even fatal. Viral vectors, especially retroviruses, can also cause insertional mutagenesis and oncogenesis.1 Finally, viruses can naturally mutate, potentially spontaneously recovering their replicative capabilities and/or their virulence. Care must be taken that viruses are handled appropriately by trained personnel and that contacted surfaces, instruments, and equipment are disinfected with virolytic agents.

Different viruses require different working environment safety precautions, and these are standardized as biosafety levels (BSL). BSL-1 criteria are appropriate for work with “defined and characterized strains of viable microorganisms not known to consistently cause disease in healthy adult humans.1” BSL-2 criteria is designed for working with “any human-derived blood, body fluids, tissues, or primary human cell lines where the presence of an infectious agent may be unknown.1” BSL-3 entails the use of primary and secondary barriers to “protect personnel in contiguous areas, the community, and the environment from exposure to potentially infectious aerosols.1” Finally, BSL-4 standards apply when working with “dangerous and exotic agents that pose a high individual risk of life-threatening disease, which may be transmitted via the aerosol route and for which there is no available vaccine or therapy.1” Most of the viral vectors used for research are classified as requiring BSL-1 (adeno-associated viruses (AAVs)) or BSL-2 (retroviruses, lentiviruses, adenoviruses, and herpes simplex viruses (HSVs)) safety precautions.

1. "Section III-Principles of Biosafety". Biosafety in Microbiological and Biomedical Laboratories, 5th ed. U.S. Department of Health and Human Services. December 2009. pp. 22-28.