Vaccinia virus is a research tool used in a variety of biomedical applications but it can be a human pathogen. Vaccinia virus is the leading agent of laboratory-acquired poxvirus infections through percutaneous injury; ocular contact; contact with infected animals or aerosols. Laboratory-acquired infections with standard, mutant, or bioengineered forms of vaccinia virus have occurred, even in previously vaccinated persons. Use of attenuated vaccinia strains can reduce risk.
Highly Attenuated Vaccinia Strains
Strains that are highly attenuated (see table below) are typically unable to replicate or replicate poorly in human cells. Vaccination is not recommended for laboratory experiments with highly attenuated vaccinia strains so long as no other orthopox viruses are in use.
| Highly Attenuated Vaccinia Strain | Biosafety Level | Derived from: | Vaccination Recommended? |
|---|---|---|---|
| MVA | 2 | Vaccinia virus (Ankara) | No |
| NYVAC | 1 | Vaccinia virus (Copenhagen) | No |
| TROVAC | 1 | Fowlpox virus | No |
| ALVAC | 1 | Canarypox virus | No |
Non-Highly Attenuated Vaccinia Strains
A vaccinia strain is considered non-highly attenuated if the virus maintains its capacity to replicate productively in mammalian cells (see the table below); pre-exposure vaccination can prevent or minimize the impact of accidental laboratory exposure. The CDC recommends vaccination every 10 years for laboratory workers in the United States who have any contact with non-highly attenuated vaccinia strains. However, individuals who are pregnant; breastfeeding; have skin conditions such as eczema or atopic dermatitis; or those with altered immune systems are at increased risk from the vaccine, and should not be vaccinated.
| Non-Highly Attenuated Vaccinia Strain | Biosafety Level | Vaccination Recommended? |
|---|---|---|
| WR (Western Reserve, mouse neuroadapted derivative) | 2 | Yes |
| NYCBOH (New York City Board of Health) | 2 | Yes |
| Copenhagen | 2 | Yes |
| Temple of Heaven | 2 | Yes |
| Lister | 2 | Yes |
Laboratory Safety
The use of BSL-2 or ABSL-2 practices and facilities are required for the manipulation of viruses or animals infected with non-highly attenuated strains. In addition to performing procedures inside a certified biological safety cabinet and avoidance of sharps and aerosol generating procedures, the use of double gloves and eye protection is recommended to minimize risk of infection.
Policy Statement:
- Personnel with potential exposure to non-highly attenuated vaccinia strains are required to complete an online vaccinia educational module which describes the risks, recommended precautions, symptoms of infection, and other important considerations associated with vaccinia use.
- Personnel who are potentially exposed to non-highly attenuated strains of vaccinia must receive medical counseling from UVA-WorkMed prior to engaging in activities that may result in exposure to vaccinia. The IBC may withhold protocol approval until evidence of medical counseling is provided. The UVA IBC recommends current vaccinia vaccination for personnel who may be potentially exposed to cultures or animals infected with non-highly attenuated strains of vaccinia and recombinant vectors derived from such strains.
Principal Investigators are ultimately responsible for assessing risk and providing a safe laboratory environment at all times. UVA-WorkMed will notify Principal Investigators when medically counseled personnel do not receive vaccination for any reason. In such cases, Principal Investigators are advised to consult with appropriate University resources (e.g. UVA-WorkMed, EHS Biosafety, Human Resources, etc.) for assistance in determining whether to alter or restrict work assignments; enhance safety practices; or prohibit laboratory access in order to maintain the safety of laboratory personnel under his or her supervision.
References
MacNeil, A., Reynolds, M., Damon, I., 2009. Risks associated with vaccinia virus in the laboratory. Virology 385 1-4.
Cornell University. Cornell University Biosafety Committee Policy and Procedures on Use of Vaccinia Virus and Research Applications. Accessed May 1 2014
Sutter, G., Moss, B., 1992. Nonreplicating vaccinia vector efficiently expresses recombinant genes. Proc. Natl. Acad. Sci. 89 (22), 10847-10851.
Meechan, P.J., Potts, J. (eds) 2020. Biosafety in Microbiological and Biomedical Laboratories (BMBL), 6th Edition, US Government Printing Office, Washington, D.C.
NIH Guidelines for Research Involving Recombinant or Synthetic Nucleic Acid Molecules
CDC. Vaccinia (Smallpox) Vaccine: Recommendations of the Immunization Practices Advisory (ACIP), 2001. MMWR, 2001; 50 (No. RR-10).
Vaccinia Vaccination Policy Review
Most recent IBC review of the Vaccinia Vaccination Policy was February 2023.