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

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Part of the book series: Methods in Molecular Biology ((MIMB,volume 2023))

Abstract

Vaccinia virus, 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 vaccinia viruses in laboratories around the world 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 vaccinia virus and reviews published cases of accidental laboratory infections with poxviruses.

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.

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References

  1. Moss B (2013) Poxviridae: the viruses and their replication. In: Knipe DM, Howley PM, Cohen JI et al (eds) Fields virology, 6th edn. Wolters Kluwer/Lippincott Williams & Wilkins Health, Philadelphia, PA, pp 2129–2159

    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  CAS  PubMed  Google Scholar 

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

    Article  CAS  PubMed  Google Scholar 

  4. Moss B (1996) Genetically engineered poxviruses for recombinant gene expression, vaccination, and safety. Proc Natl Acad Sci U S A 93(21):11341–11348

    Article  CAS  PubMed  PubMed Central  Google Scholar 

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

    Article  CAS  PubMed  Google Scholar 

  6. Hawkes N (1979) Smallpox death in Britain challenges presumption of laboratory safety. Science 203(4383):855–856

    Article  CAS  PubMed  Google Scholar 

  7. CDC (1985) Recommendations of the immunization practices advisory committee smallpox vaccine. MMWR Morb Mortal Wkly Rep 34:341–342

    Google Scholar 

  8. CDC (1991) Vaccinia (smallpox) vaccine. Recommendations of the Immunization Practices Advisory Committee (ACIP). MMWR Morb Mortal Wkly Rep 40(RR-14):1–10

    Google Scholar 

  9. CDC (2001) Vaccinia (smallpox) vaccine Recommendations of the Advisory Committee on Immunization Practices (ACIP), 2001. MMWR Morb Mortal Wkly Rep 50(RR10):1–25

    Google Scholar 

  10. 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(RR-7):1–16

    Google Scholar 

  11. CDC (2003) Supplemental recommendations on adverse events following smallpox vaccine in the pre-event vaccination program: recommendations of the Advisory Committee on Immunization Practices. MMWR Morb Mortal Wkly Rep 52(13):282–284

    Google Scholar 

  12. Petersen BW, Harms TJ, Reynolds MG, Harrison LH (2016) Use of vaccinia virus smallpox vaccine in laboratory and health care personnel at risk for occupational exposure to orthopoxviruses—recommendations of the Advisory Committee on Immunization Practices (ACIP), 2015. MMWR Morb Mortal Wkly Rep 65(10):257–262. https://doi.org/10.15585/mmwr.mm6510a2

    Article  PubMed  Google Scholar 

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

    Article  CAS  PubMed  Google Scholar 

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

    Article  CAS  PubMed  Google Scholar 

  15. 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(8):582–586

    Article  CAS  PubMed  Google Scholar 

  16. 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(6):724–726

    PubMed  PubMed Central  Google Scholar 

  17. 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(3):356–358

    Article  CAS  PubMed  Google Scholar 

  18. Loeb M, Zando I, Orvidas MC, Bialachowski A, Groves D, Mahoney J (2003) Laboratory-acquired vaccinia infection. Can Commun Dis Rep 29(15):134–136

    CAS  PubMed  Google Scholar 

  19. Wlodaver CG, Palumbo GJ, Waner JL (2004) Laboratory-acquired vaccinia infection. J Clin Virol 29(3):167–170

    Article  PubMed  Google Scholar 

  20. 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(1):134–137

    Article  PubMed  PubMed Central  Google Scholar 

  21. Peate WF (2007) Prevention of vaccinia infection in a laboratory worker. Mil Med 172(10):1117–1118

    Article  PubMed  Google Scholar 

  22. 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(11):817–819

    Article  CAS  PubMed  Google Scholar 

  23. CDC (2008) Laboratory-acquired vaccinia exposures and infections—United States, 2005–2007. MMWR Morb Mortal Wkly Rep 57(15):401–404

    Google Scholar 

  24. CDC (2009) Laboratory-acquired vaccinia virus infection—Virginia, 2008. MMWR Morb Mortal Wkly Rep 58(29):797–800

    Google Scholar 

  25. Senanayake SN (2009) Needlestick injury with smallpox vaccine. Med J Aust 191(11-12):657

    PubMed  Google Scholar 

  26. CDC (2009) Human vaccinia infection after contact with a raccoon rabies vaccine bait—Pennsylvania, 2009. MMWR Morb Mortal Wkly Rep 58(43):1204–1207

    Google Scholar 

  27. McCollum AM, Austin C, Nawrocki J, Howland J, Pryde J, Vaid A, Holmes D, Weil MR, Li Y, Wilkins K, Zhao H, Smith SK, Karem K, Reynolds MG, Damon IK (2012) Investigation of the first laboratory-acquired human cowpox virus infection in the United States. J Infect Dis 206(1):63–68. https://doi.org/10.1093/infdis/jis302

    Article  CAS  PubMed  Google Scholar 

  28. Riyesh T, Karuppusamy S, Bera BC, Barua S, Virmani N, Yadav S, Vaid RK, Anand T, Bansal M, Malik P, Pahuja I, Singh RK (2014) Laboratory-acquired buffalopox virus infection, India. Emerg Infect Dis 20(2):324–326. https://doi.org/10.3201/eid2002.130358

    Article  PubMed  Google Scholar 

  29. Hsu CH, Farland J, Winters T, Gunn J, Caron D, Evans J, Osadebe L, Bethune L, McCollum AM, Patel N, Wilkins K, Davidson W, Petersen B, Barry MA, Centers for Disease Control and Prevention (2015) Laboratory-acquired vaccinia virus infection in a recently immunized person—Massachusetts, 2013. MMWR Morb Mortal Wkly Rep 64(16):435–438

    PubMed  PubMed Central  Google Scholar 

  30. Office of Recombinant DNA Activities; recombinant DNA research: action under the guidelines. National Institutes of Health (NIH), PHS, DHHS (2016) Notice of action under the NIH Guidelines for Research Involving Recombinant DNA Molecules (NIH Guidelines). Fed Regist 81 (https://osp.od.nih.gov/wp-content/uploads/NIH_Guidelines.html)

  31. Niederkorn JY (2002) Immune privilege in the anterior chamber of the eye. Crit Rev Immunol 22(1):13–46

    Article  CAS  PubMed  Google Scholar 

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

    Article  CAS  PubMed  Google Scholar 

  33. Jonczy EA, Daly J, Kotwal GJ (2000) A novel approach using an attenuated recombinant vaccinia virus to test the antipoxviral effects of hand soaps. Antiviral Res 45(2):149–153

    Article  CAS  PubMed  Google Scholar 

  34. Richmond JY, RW MK (eds) (1999) Biosafety in microbiological and biomedical laboratories. HHS publication; no. (CDC) 93-8395, 4th edn. U.S. Department of Health and Human Services, PHS, CDC, NIH, Washington DC

    Google Scholar 

  35. Block SS (ed) (2001) Disinfection, sterilization, and preservation, 5th edn. Lippincott Williams & Wilkins, Philadelphia

    Google Scholar 

  36. 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(7):624–628

    Article  CAS  PubMed  Google Scholar 

  37. CDC (2008) Notice to readers: newly licensed smallpox vaccine to replace old smallpox vaccine. MMWR Morb Mortal Wkly Rep 57(8):207–208

    Google Scholar 

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

    Article  Google Scholar 

  39. Wenzel RP, Nettleman MD (1989) Smallpox vaccination for investigators using vaccinia recombinants. Lancet 2(8663):630–631

    Article  CAS  PubMed  Google Scholar 

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

    Google Scholar 

  41. Baxby D (1993) Indications for smallpox vaccination: policies still differ. Vaccine 11(4):395–396

    Article  CAS  PubMed  Google Scholar 

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

    Article  CAS  Google Scholar 

  43. Isaacs SN (2002) Critical evaluation of smallpox vaccination for laboratory workers. Occup Environ Med 59(9):573–574

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  44. 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  CAS  PubMed  Google Scholar 

  45. 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  CAS  PubMed  Google Scholar 

  46. Poland GA, Grabenstein JD, Neff JM (2005) The US smallpox vaccination program: a review of a large modern era smallpox vaccination implementation program. Vaccine 23(17–18):2078–2081

    Article  PubMed  Google Scholar 

  47. 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(8):1133–1140

    Article  PubMed  Google Scholar 

  48. CDC (2004) Secondary and tertiary transfer of vaccinia virus among U.S. military personnel—United States and worldwide, 2002–2004. MMWR Morb Mortal Wkly Rep 53(5):103–105

    Google Scholar 

  49. CDC (2007) Household transmission of vaccinia virus from contact with a military smallpox vaccinee–Illinois and Indiana, 2007. MMWR Morb Mortal Wkly Rep 56(19):478–481

    Google Scholar 

  50. CDC (2007) Vulvar vaccinia infection after sexual contact with a military smallpox vaccinee–Alaska, 2006. MMWR Morb Mortal Wkly Rep 56(17):417–419

    Google Scholar 

  51. CDC (2010) Vaccinia virus infection after sexual contact with a military smallpox vaccinee–Washington, 2010. MMWR Morb Mortal Wkly Rep 59(25):773–775

    Google Scholar 

  52. 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(4):718–721

    Article  PubMed  PubMed Central  Google Scholar 

  53. 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(4):730–733

    Article  PubMed  PubMed Central  Google Scholar 

  54. Advisory Committee on Dangerous Pathogens and Advisory Committee on Genetic Modifications (1990; re-issued 2011) Vaccination of laboratory workers handling vaccinia and related poxviruses infectious for humans. HMSO Publications Center, London (http://www.hse.gov.uk/pUbns/priced/acdp-acgm-vaccine.pdf)

  55. Fulginiti VA (2003) The risks of vaccinia in laboratory workers. J Invest Dermatol 120(3):viii

    Article  CAS  PubMed  Google Scholar 

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

    Article  CAS  PubMed  Google Scholar 

  57. Greenberg RN, Kennedy JS (2008) ACAM2000: a newly licensed cell culture-based live vaccinia smallpox vaccine. Expert Opin Investig Drugs 17(4):555–564

    Article  CAS  PubMed  Google Scholar 

  58. Kennedy JS, Greenberg RN (2009) IMVAMUNE: modified vaccinia Ankara strain as an attenuated smallpox vaccine. Expert Rev Vaccines 8(1):13–24

    Article  CAS  PubMed  Google Scholar 

  59. 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(5):1817–1822

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  60. Chinsangaram J, Honeychurch KM, Tyavanagimatt SR, Leeds JM, Bolken TC, Jones KF, Jordan R, Marbury T, Ruckle J, Mee-Lee D, Ross E, Lichtenstein I, Pickens M, Corrado M, Clarke JM, Frimm AM, Hruby DE (2012) Safety and pharmacokinetics of the anti-orthopoxvirus compound ST-246 following a single daily oral dose for 14 days in human volunteers. Antimicrob Agents Chemother 56(9):4900–4905. https://doi.org/10.1128/AAC.00904-12

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  61. 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(12):2740–2762

    Article  Google Scholar 

  62. 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(1):75–77

    Article  Google Scholar 

  63. Isaacs SN (2004) Vaccinia virus and poxvirology: Methods and protocols, Methods in Molecular Biology. Humana Press, c2004, Totowa, NJ

    Book  Google Scholar 

  64. Isaacs SN (2012) Working safely with vaccinia virus: laboratory technique and review of published cases of accidental laboratory infections. Methods Mol Biol 890:1–22. https://doi.org/10.1007/978-1-61779-876-4_1

    Article  CAS  PubMed  Google Scholar 

  65. CDC (2009) Progressive vaccinia in a military smallpox vaccinee—United States, 2009. MMWR Morb Mortal Wkly Rep 58(19):532–536

    Google Scholar 

  66. Vora S, Damon I, Fulginiti V, Weber SG, Kahana M, Stein SL, Gerber SI, Garcia-Houchins S, Lederman E, Hruby D, Collins L, Scott D, Thompson K, Barson JV, Regnery R, Hughes C, Daum RS, Li Y, Zhao H, Smith S, Braden Z, Karem K, Olson V, Davidson W, Trindade G, Bolken T, Jordan R, Tien D, Marcinak J (2008) Severe eczema vaccinatum in a household contact of a smallpox vaccinee. Clin Infect Dis 46(10):1555–1561. https://doi.org/10.1086/587668

    Article  PubMed  Google Scholar 

  67. Cono J, Casey CG, Bell DM (2003) Smallpox vaccination and adverse reactions. Guidance for clinicians. MMWR Recomm Rep 52(RR-4):1–28

    PubMed  Google Scholar 

  68. CDC (2003) Update: cardiac-related events during the civilian smallpox vaccination program—United States, 2003. MMWR Morb Mortal Wkly Rep 52(21):492–496

    Google Scholar 

  69. 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(24):3283–3289

    Article  PubMed  Google Scholar 

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

    CAS  PubMed  PubMed Central  Google Scholar 

  71. 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

    CAS  PubMed  PubMed Central  Google Scholar 

  72. 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(1):85–88

    CAS  PubMed  Google Scholar 

  73. Holt RK, Walker BK, Ruff AJ (2002) Horizontal transmission of recombinant vaccinia virus in strain 13 guinea pigs. Contemp Top Lab Anim Sci 41(2):57–60

    CAS  PubMed  Google Scholar 

  74. Engler RJ, Kenner J, Leung DY (2002) Smallpox vaccination: risk considerations for patients with atopic dermatitis. J Allergy Clin Immunol 110(3):357–365

    Article  CAS  PubMed  Google Scholar 

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Acknowledgment

The author is supported by the Philadelphia Veterans Affairs Medical Center (recently renamed, Corporal Michael J. Crescenz VA Medical Center) and by NIH grants R21 AI117100, R44 AI115759, and R44 AI125005.

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Correspondence to Stuart N. Isaacs .

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Isaacs, S.N. (2019). Working Safely with Vaccinia Virus: Laboratory Technique and Review of Published Cases of Accidental Laboratory Infections with Poxviruses. In: Mercer, J. (eds) Vaccinia Virus. Methods in Molecular Biology, vol 2023. Humana, New York, NY. https://doi.org/10.1007/978-1-4939-9593-6_1

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  • DOI: https://doi.org/10.1007/978-1-4939-9593-6_1

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