Skip to main content
SpringerLink
Log in

Working Safely with Vaccinia Virus: Laboratory Technique and Review of Published Cases of Accidental Laboratory Infections

  • Protocol
  • First Online:
Vaccinia Virus and Poxvirology

Part of the book series: Methods in Molecular Biology ((MIMB,volume 890))

Abstract

Vaccinia virus (VACV), the prototype orthopoxvirus, is widely used in the laboratory as a model system to study various aspects of viral biology and virus–host interactions, as a protein expression system, as a vaccine vector, and as an oncolytic agent. The ubiquitous use of VACVs in the laboratory raises certain safety concerns because the virus can be a pathogen in individuals with immunological and dermatological abnormalities, and on occasion can cause serious problems in normal hosts. This chapter reviews standard operating procedures when working with VACV and reviews published cases on accidental laboratory infections.

The views expressed in this chapter are solely those of the author and do not necessarily reflect the position or policy of the Department of Veterans Affairs or the University of Pennsylvania.

This is a preview of subscription content, log in via an institution to check access.

Access this chapter

Log in via an institution
Protocol
USD 49.95
Price excludes VAT (USA)
  • Available as PDF
  • Read on any device
  • Instant download
  • Own it forever
eBook
USD 84.99
Price excludes VAT (USA)
  • Available as EPUB and PDF
  • Read on any device
  • Instant download
  • Own it forever
Softcover Book
USD 159.00
Price excludes VAT (USA)
  • Compact, lightweight edition
  • Dispatched in 3 to 5 business days
  • Free shipping worldwide - see info
Hardcover Book
USD 109.99
Price excludes VAT (USA)
  • Durable hardcover edition
  • Dispatched in 3 to 5 business days
  • Free shipping worldwide - see info

Tax calculation will be finalised at checkout

Purchases are for personal use only

Institutional subscriptions

Similar content being viewed by others

References

  1. Moss B (2007) Poxviridae: the viruses and their replication. In: Knipe DM, Howley PM (eds) Fields’ virology. Wolters Kluwer Health/Lippincott Williams & Wilkins, Philadelphia, Chapter 74

    Google Scholar 

  2. Seet BT, Johnston JB, Brunetti CR, Barrett JW, Everett H, Cameron C, Sypula J, Nazarian SH, Lucas A, McFadden G (2003) Poxviruses and immune evasion. Annu Rev Immunol 21:377–423

    Article  PubMed  CAS  Google Scholar 

  3. Haga IR, Bowie AG (2005) Evasion of innate immunity by vaccinia virus. Parasitology 130:S11–S25

    Article  PubMed  CAS  Google Scholar 

  4. Moss B (1996) Genetically engineered poxviruses for recombinant gene expression, vaccination, and safety. Proc Natl Acad Sci USA 93:11341–11348

    Article  PubMed  CAS  Google Scholar 

  5. Carroll MW, Moss B (1997) Poxviruses as expression vectors. Curr Opin Biotechnol 8:573–577

    Article  PubMed  CAS  Google Scholar 

  6. CDC (1985) Recommendations of the Immunization Practices Advisory Committee smallpox vaccine. Morb Mortal Wkly Rep 34:341–342

    Google Scholar 

  7. CDC (1991) Vaccinia (smallpox) vaccine. Recommendations of the Immunization Practices Advisory Committee (ACIP). Morb Mortal Wkly Rep 40:1–10

    Google Scholar 

  8. CDC (2001) Vaccinia (smallpox) vaccine recommendations of the Advisory Committee on Immunization Practices (ACIP), 2001. Morb Mortal Wkly Rep 50:1–25

    Google Scholar 

  9. CDC (2003) Recommendations for using smallpox vaccine in a pre-event vaccination program. Supplemental recommendations of the Advisory Committee on Immunization Practices (ACIP) and the Healthcare Infection Control Practices Advisory Committee (HICPAC). MMWR Recomm Rep 52:1–16

    Google Scholar 

  10. CDC (2003) Supplemental recommendations on adverse events following smallpox vaccine in the pre-event vaccination program: recommendations of the Advisory Committee on Immunization Practices. Morb Mortal Wkly Rep 52:282–284

    Google Scholar 

  11. Jones L, Ristow S, Yilma T, Moss B (1986) Accidental human vaccination with vaccinia virus expressing nucleoprotein gene. Nature 319:543

    Article  PubMed  CAS  Google Scholar 

  12. Openshaw PJ, Alwan WH, Cherrie AH, Record FM (1991) Accidental infection of laboratory worker with recombinant vaccinia virus. Lancet 338:459

    Article  PubMed  CAS  Google Scholar 

  13. Rupprecht CE, Blass L, Smith K, Orciari LA, Niezgoda M, Whitfield SG, Gibbons RV, Guerra M, Hanlon CA (2001) Human infection due to recombinant vaccinia-rabies glycoprotein virus. N Engl J Med 345:582–586

    Article  PubMed  CAS  Google Scholar 

  14. Moussatche N, Tuyama M, Kato SE, Castro AP, Njaine B, Peralta RH, Peralta JM, Damaso CR, Barroso PF (2003) Accidental infection of laboratory worker with vaccinia virus. Emerg Infect Dis 9:724–726

    PubMed  Google Scholar 

  15. Mempel M, Isa G, Klugbauer N, Meyer H, Wildi G, Ring J, Hofmann F, Hofmann H (2003) Laboratory acquired infection with recombinant vaccinia virus containing an immunomodulating construct. J Invest Dermatol 120:356–358

    Article  PubMed  CAS  Google Scholar 

  16. Loeb M, Zando I, Orvidas MC, Bialachowski A, Groves D, Mahoney J (2003) Laboratory-acquired vaccinia infection. Can Commun Dis Rep 29:134–136

    PubMed  CAS  Google Scholar 

  17. Wlodaver CG, Palumbo GJ, Waner JL (2004) Laboratory-acquired vaccinia infection. J Clin Virol 29:167–170

    Article  PubMed  Google Scholar 

  18. Lewis FM, Chernak E, Goldman E, Li Y, Karem K, Damon IK, Henkel R, Newbern EC, Ross P, Johnson CC (2006) Ocular vaccinia infection in laboratory worker, Philadelphia, 2004. Emerg Infect Dis 12:134–137

    Article  PubMed  Google Scholar 

  19. Peate WF (2007) Prevention of vaccinia infection in a laboratory worker. Mil Med 172:1117–1118

    PubMed  Google Scholar 

  20. Eisenbach C, Neumann-Haefelin C, Freyse A, Korsukewitz T, Hoyler B, Stremmel W, Thimme R, Encke J (2007) Immune responses against HCV-NS3 after accidental infection with HCV-NS3 recombinant vaccinia virus. J Viral Hepat 14:817–819

    Article  PubMed  CAS  Google Scholar 

  21. CDC (2008) Laboratory-acquired vaccinia exposures and infections—United States, 2005–2007. Morb Mortal Wkly Rep 57:401–404

    Google Scholar 

  22. CDC (2009) Laboratory-acquired vaccinia virus infection—Virginia, 2008. Morb Mortal Wkly Rep 58:797–800

    Google Scholar 

  23. Senanayake SN (2009) Needlestick injury with smallpox vaccine. Med J Aust 191:657

    PubMed  Google Scholar 

  24. CDC (2009) Human vaccinia infection after contact with a raccoon rabies vaccine bait—Pennsylvania, 2009. Morb Mortal Wkly Rep 58:1204–1207

    Google Scholar 

  25. NIH (1996) Modifications to NIH vaccinia immunization policy. U.S. Department of Health and Human Services, Bethesda, MD

    Google Scholar 

  26. Niederkorn JY (2002) Immune privilege in the anterior chamber of the eye. Crit Rev Immunol 22:13–46

    Article  PubMed  CAS  Google Scholar 

  27. Ruben FL, Lane JM (1970) Ocular vaccinia. An epidemiologic analysis of 348 cases. Arch Ophthal 84:45–48

    Article  PubMed  CAS  Google Scholar 

  28. Jonczy EA, Daly J, Kotwal GJ (2000) A novel approach using an attenuated recombinant vaccinia virus to test the antipoxviral effects of handsoaps. Antiviral Res 45:149–153

    Article  PubMed  CAS  Google Scholar 

  29. Richmond JY, McKinney RW (1999). In: HHS publication; no. (CDC) 93-8395. U.S. Depart­ment of Health and Human Services, PHS, CDC, NIH, Washington, DC

    Google Scholar 

  30. Block SS (2001) Disinfection, sterilization, and preservation. Lippincott Williams & Wilkins, Philadelphia

    Google Scholar 

  31. Espy MJ, Uhl JR, Sloan LM, Rosenblatt JE, Cockerill FR 3rd, Smith TF (2002) Detection of vaccinia virus, herpes simplex virus, varicella-zoster virus, and Bacillus anthracis DNA by LightCycler polymerase chain reaction after autoclaving: implications for biosafety of bioterrorism agents. Mayo Clin Proc 77:624–628

    Article  PubMed  CAS  Google Scholar 

  32. CDC (2008) Notice to readers: newly licensed smallpox vaccine to replace old smallpox vaccine. Morb Mortal Wkly Rep 57:207–208

    Google Scholar 

  33. Baxby D (1989) Smallpox vaccination for investigators. Lancet 2:919

    Article  Google Scholar 

  34. Wenzel RP, Nettleman MD (1989) Smallpox vaccination for investigators using vaccinia recombinants. Lancet 2:630–631

    Article  PubMed  CAS  Google Scholar 

  35. Perry GF (1992) Occupational medicine forum. J Occup Med 34:757

    Google Scholar 

  36. Baxby D (1993) Indications for smallpox vaccination: policies still differ. Vaccine 11: 395–396

    Article  PubMed  CAS  Google Scholar 

  37. Williams NR, Cooper BM (1993) Counselling of workers handling vaccinia virus. Occup Med (Oxf) 43:125–127

    Article  CAS  Google Scholar 

  38. Isaacs SN (2002) Critical evaluation of smallpox vaccination for laboratory workers. Occup Environ Med 59:573–574

    Article  PubMed  CAS  Google Scholar 

  39. Lane JM, Ruben FL, Neff JM, Millar JD (1969) Complications of smallpox vaccination, 1968. National surveillance in the United States. New Engl J Med 281:1201–1208

    Article  PubMed  CAS  Google Scholar 

  40. Lane JM, Ruben FL, Neff JM, Millar JD (1970) Complications of smallpox vaccination, 1968: results of ten statewide surveys. J Infect Dis 122:303–309

    Article  PubMed  CAS  Google Scholar 

  41. Grabenstein JD, Winkenwerder W Jr (2003) US military smallpox vaccination program experience. JAMA 289:3278–3282

    Article  PubMed  Google Scholar 

  42. CDC (2004) Update: adverse events following civilian smallpox vaccination—United States, 2003. Morb Mortal Wkly Rep 53:106–107

    Google Scholar 

  43. Baggs J, Chen RT, Damon IK, Rotz L, Allen C, Fullerton KE, Casey C, Nordenberg D, Mootrey G (2005) Safety profile of smallpox vaccine: insights from the laboratory worker smallpox vaccination program. Clin Infect Dis 40:1133–1140

    Article  PubMed  Google Scholar 

  44. CDC (2004) Secondary and tertiary transfer of vaccinia virus among U.S. military personnel—United States and worldwide, 2002–2004. Morb Mortal Wkly Rep 53:103–105

    Google Scholar 

  45. CDC (2007) Household transmission of vaccinia virus from contact with a military smallpox vaccinee—Illinois and Indiana, 2007. Morb Mortal Wkly Rep 56:478–481

    Google Scholar 

  46. CDC (2007) Vulvar vaccinia infection after sexual contact with a military smallpox vaccinee–Alaska, 2006. Morb Mortal Wkly Rep 56:417–419

    Google Scholar 

  47. CDC (2010) Vaccinia virus infection after sexual contact with a military smallpox vaccinee—Washington, 2010. Morb Mortal Wkly Rep 59:773–775

    Google Scholar 

  48. Young GE, Hidalgo CM, Sullivan-Frohm A, Schult C, Davis S, Kelly-Cirino C, Egan C, Wilkins K, Emerson GL, Noyes K, Blog D (2011) Secondary and tertiary transmission of vaccinia virus from US military service member. Emerg Infect Dis 17:718–721

    Article  PubMed  Google Scholar 

  49. Hughes CM, Blythe D, Li Y, Reddy R, Jordan C, Edwards C, Adams C, Conners H, Rasa C, Wilby S, Russell J, Russo KS, Somsel P, Wiedbrauk DL, Dougherty C, Allen C, Frace M, Emerson G, Olson VA, Smith SK, Braden Z, Abel J, Davidson W, Reynolds M, Damon IK (2011) Vaccinia virus infections in martial arts gym, Maryland, USA, 2008. Emerg Infect Dis 17:730–733

    Article  PubMed  Google Scholar 

  50. Advisory Committee on Dangerous Patho­gens and Advisory Committee on Genetic Modifications (1990) HMSO Publications Center, London, pp 1–16

    Google Scholar 

  51. Fulginiti VA (2003) The risks of vaccinia in laboratory workers. J Invest Dermatol 120:viii

    Article  PubMed  CAS  Google Scholar 

  52. MacNeil A, Reynolds MG, Damon IK (2009) Risks associated with vaccinia virus in the laboratory. Virology 385:1–4

    Article  PubMed  CAS  Google Scholar 

  53. Greenberg RN, Kennedy JS (2008) ACAM2000: a newly licensed cell culture-based live vaccinia smallpox vaccine. Expert Opin Investig Drugs 17:555–664

    Article  PubMed  CAS  Google Scholar 

  54. Kennedy JS, Greenberg RN (2009) IMVAMUNE: modified vaccinia Ankara strain as an attenuated smallpox vaccine. Expert Rev Vaccines 8:13–24

    Article  PubMed  CAS  Google Scholar 

  55. Jordan R, Goff A, Frimm A, Corrado ML, Hensley LE, Byrd CM, Mucker E, Shamblin J, Bolken TC, Wlazlowski C, Johnson W, Chapman J, Twenhafel N, Tyavanagimatt S, Amantana A, Chinsangaram J, Hruby DE, Huggins J (2009) ST-246 antiviral efficacy in a nonhuman primate monkeypox model: determination of the minimal effective dose and human dose justification. Antimicrob Agents Chemother 53:1817–1822

    Article  PubMed  CAS  Google Scholar 

  56. Lanier R, Trost L, Tippin T, Lampert B, Robertson A, Foster S, Rose M, Painter W, O’Mahony R, Almond M, Painter G (2010) Development of CMX001 for the treatment of poxvirus infections. Viruses 1:2740–2762

    Article  CAS  Google Scholar 

  57. Benzekri N, Goldman E, Lewis F, Johnson CC, Reynolds SM, Reynolds MG, Damon IK (2010) Laboratory worker knowledge, attitudes and practices towards smallpox vaccine. Occup Med (Lond) 60:75–77

    Article  Google Scholar 

  58. Isaacs SN (2004) Vaccinia virus and poxvirology: methods and protocols. Humana Press, Totowa, NJ

    Book  Google Scholar 

  59. CDC (2009) Progressive vaccinia in a military smallpox vaccinee—United States, 2009. Morb Mortal Wkly Rep 58:532–536

    Google Scholar 

  60. Cono J, Casey CG, Bell DM (2003) Smallpox vaccination and adverse reactions. Guidance for clinicians. MMWR Recomm Rep 52:1–28

    PubMed  Google Scholar 

  61. CDC (2003) Update: cardiac-related events during the civilian smallpox vaccination program—United States, 2003. Morb Mortal Wkly Rep 52:492–496

    Google Scholar 

  62. Halsell JS, Riddle JR, Atwood JE, Gardner P, Shope R, Poland GA, Gray GC, Ostroff S, Eckart RE, Hospenthal DR, Gibson RL, Grabenstein JD, Arness MK, Tornberg DN (2003) Myopericarditis following smallpox vaccination among vaccinia-naive US military personnel. JAMA 289:3283–3289

    Article  PubMed  Google Scholar 

  63. Briody BA (1959) Response of mice to ectromelia and vaccinia viruses. Bacteriol Rev 23:61–95

    PubMed  CAS  Google Scholar 

  64. Lee SL, Roos JM, McGuigan LC, Smith KA, Cormier N, Cohen LK, Roberts BE, Payne LG (1992) Molecular attenuation of vaccinia virus: mutant generation and animal characterization. J Virol 66:2617–2630

    PubMed  CAS  Google Scholar 

  65. Gaertner DJ, Batchelder M, Herbst LH, Kaufman HL (2003) Administration of vaccinia virus to mice may cause contact or bedding sentinel mice to test positive for orthopoxvirus antibodies: case report and follow-up investigation. Comp Med 53:85–88

    PubMed  CAS  Google Scholar 

  66. Holt RK, Walker BK, Ruff AJ (2002) Horizontal transmission of recombinant vaccinia virus in strain 13 guinea pigs. Contemp Top Lab Anim Sci 41:57–60

    PubMed  CAS  Google Scholar 

  67. Engler RJ, Kenner J, Leung DY (2002) Smallpox vaccination: risk considerations for patients with atopic dermatitis. J Allergy Clin Immunol 110:357–365

    Article  PubMed  CAS  Google Scholar 

Download references

Acknowledgments

I thank Edward Alexander for helpful discussions. The author is supported by the Philadelphia Veterans Affairs Medical Center, NIH grants U01 AI077913 and U01 AI066333, and the Middle Atlantic Regional Center of Excellence in Biodefense and Emerging Infectious Diseases (U54 AI057168).

Author information

Authors and Affiliations

  1. Division of Infectious Diseases, Department of Medicine, University of Pennsylvania and the Philadelphia VA Medical Center, Philadelphia, PA, USA

    Stuart N. Isaacs

Authors
  1. Stuart N. Isaacs
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Stuart N. Isaacs .

Editor information

Editors and Affiliations

  1. School of Medicine and the Philadelphia, Division of Infectious Disease, University of Pennsylvania, Johnson Pavilion 502, Philadelphia, 19104-6073, Pennsylvania, USA

    Stuart N. Isaacs

Rights and permissions

Reprints and permissions

Copyright information

© 2012 Springer Science+Business Media, LLC

About this protocol

Cite this protocol

Isaacs, S.N. (2012). Working Safely with Vaccinia Virus: Laboratory Technique and Review of Published Cases of Accidental Laboratory Infections. In: Isaacs, S. (eds) Vaccinia Virus and Poxvirology. Methods in Molecular Biology, vol 890. Humana Press, Totowa, NJ. https://doi.org/10.1007/978-1-61779-876-4_1

Download citation

  • DOI: https://doi.org/10.1007/978-1-61779-876-4_1

  • Published:

  • Publisher Name: Humana Press, Totowa, NJ

  • Print ISBN: 978-1-61779-875-7

  • Online ISBN: 978-1-61779-876-4

  • eBook Packages: Springer Protocols

Publish with us

Policies and ethics

Search

Navigation