Official reprint from UpToDate®
www.uptodate.com ©2017 UpToDate, Inc. and/or its affiliates. All Rights Reserved.

Vaccinia virus in the research setting

Stuart N Isaacs, MD
Harvey M Friedman, MD
Section Editor
Martin S Hirsch, MD
Deputy Editor
Jennifer Mitty, MD, MPH


Vaccinia virus was the live poxvirus used throughout the world as the vaccine against smallpox. With the worldwide eradication of smallpox, routine vaccination with vaccinia virus is no longer performed. However, after the anthrax bioterrorism attack in October 2001, there was a debate about the advisability of reinitiating routine vaccination against smallpox [1,2].

Even prior to the potential need to revaccinate an at-risk population due to concerns about bioterrorism with smallpox, vaccinia virus has remained important to understand because of its widespread use as an expression vector in research laboratories and because of its potential use as a vector for recombinant vaccines or as an oncolytic agent. In addition, the military continues to routinely vaccinate recruits against smallpox.

Infectious diseases clinicians may see patients with complications from smallpox vaccination or be asked about the advisability of vaccination for occupational exposure to vaccinia virus or other orthopoxviruses. Since routine vaccination was stopped in the United States in the 1970s, current decisions about vaccination are now made when there are an ever-expanding number of students and researchers who are working with vaccinia virus who were never vaccinated as children.

Issues related to vaccinia virus in the research setting will be reviewed here. Vaccinia virus as the smallpox vaccine to prevent smallpox is discussed separately. (See "Vaccinia virus as the smallpox vaccine".)


Controversy exists as to whether to vaccinate all researchers working with vaccinia virus [3-8] since the smallpox vaccine has had an imperfect safety record resulting in both mild and severe adverse reactions:

To continue reading this article, you must log in with your personal, hospital, or group practice subscription. For more information on subscription options, click below on the option that best describes you:

Subscribers log in here

Literature review current through: Nov 2017. | This topic last updated: Jul 24, 2017.
The content on the UpToDate website is not intended nor recommended as a substitute for medical advice, diagnosis, or treatment. Always seek the advice of your own physician or other qualified health care professional regarding any medical questions or conditions. The use of this website is governed by the UpToDate Terms of Use ©2017 UpToDate, Inc.
  1. Fauci AS. Smallpox vaccination policy--the need for dialogue. N Engl J Med 2002; 346:1319.
  2. Bicknell WJ. The case for voluntary smallpox vaccination. N Engl J Med 2002; 346:1323.
  3. Openshaw PJ, Alwan WH, Cherrie AH, Record FM. Accidental infection of laboratory worker with recombinant vaccinia virus. Lancet 1991; 338:459.
  4. Baxby D. Indications for smallpox vaccination: policies still differ. Vaccine 1993; 11:395.
  5. Wenzel RP, Nettleman MD. Smallpox vaccination for investigators using vaccinia recombinants. Lancet 1989; 2:630.
  6. Jones L, Ristow S, Yilma T, Moss B. Accidental human vaccination with vaccinia virus expressing nucleoprotein gene. Nature 1986; 319:543.
  7. Wenzel RP, Nettleman MD. Smallpox vaccination for investigators using vaccinia recombinants. Lancet 1989; 2:630.
  8. Williams NR, Cooper BM. Counselling of workers handling vaccinia virus. Occup Med (Lond) 1993; 43:125.
  9. Petersen BW, Harms TJ, Reynolds MG, Harrison LH. 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 2016; 65:257.
  10. Advisory Committee on Dangerous Pathogens, Advisory Committee on Genetic Modification. Vaccination of laboratory workers handling vaccinia and related poxviruses infectious for humans, HMSO, London 1990.
  11. Cooney EL, Collier AC, Greenberg PD, et al. Safety of and immunological response to a recombinant vaccinia virus vaccine expressing HIV envelope glycoprotein. Lancet 1991; 337:567.
  12. Dolin R, Graham BS, Greenberg SB, et al. The safety and immunogenicity of a human immunodeficiency virus type 1 (HIV-1) recombinant gp160 candidate vaccine in humans. NIAID AIDS Vaccine Clinical Trials Network. Ann Intern Med 1991; 114:119.
  13. Fulginiti VA. The risks of vaccinia in laboratory workers. J Invest Dermatol 2003; 120:viii.
  14. MacNeil A, Reynolds MG, Damon IK. Risks associated with vaccinia virus in the laboratory. Virology 2009; 385:1.
  15. Isaacs SN. Working safely with vaccinia virus: laboratory technique and review of published cases of accidental laboratory infections. Methods Mol Biol 2012; 890:1.
  16. Centers for Disease Control and Prevention (CDC). Laboratory-acquired vaccinia exposures and infections--United States, 2005-2007. MMWR Morb Mortal Wkly Rep 2008; 57:401.
  17. Centers for Disease Control and Prevention (CDC). Laboratory-acquired vaccinia virus infection--Virginia, 2008. MMWR Morb Mortal Wkly Rep 2009; 58:797.
  18. Centers for Disease Control (CDC). Contact spread of vaccinia from a National Guard vaccinee--Wisconsin. MMWR Morb Mortal Wkly Rep 1985; 34:182.
  19. Centers for Disease Control (CDC). Contact spread of vaccinia from a recently vaccinated Marine--Louisiana. MMWR Morb Mortal Wkly Rep 1984; 33:37.
  20. Centers for Disease Control (CDC). Vaccinia outbreak--Newfoundland. MMWR Morb Mortal Wkly Rep 1981; 30:453.
  21. Tack DM, Karem KL, Montgomery JR, et al. Unintentional transfer of vaccinia virus associated with smallpox vaccines: ACAM2000(®) compared with Dryvax(®). Hum Vaccin Immunother 2013; 9:1489.
  22. Vanderplasschen A, Hollinshead M, Smith GL. Antibodies against vaccinia virus do not neutralize extracellular enveloped virus but prevent virus release from infected cells and comet formation. J Gen Virol 1997; 78 ( Pt 8):2041.
  23. Buller RM, Smith GL, Cremer K, et al. Decreased virulence of recombinant vaccinia virus expression vectors is associated with a thymidine kinase-negative phenotype. Nature 1985; 317:813.
  24. Taylor G, Stott EJ, Wertz G, Ball A. Comparison of the virulence of wild-type thymidine kinase (tk)-deficient and tk+ phenotypes of vaccinia virus recombinants after intranasal inoculation of mice. J Gen Virol 1991; 72 ( Pt 1):125.
  25. Baxby D. Safety of recombinant vaccinia vaccines. Lancet 1991; 337:913.
  26. Graham BS, Belshe RB, Clements ML, et al. Vaccination of vaccinia-naive adults with human immunodeficiency virus type 1 gp160 recombinant vaccinia virus in a blinded, controlled, randomized clinical trial. The AIDS Vaccine Clinical Trials Network. J Infect Dis 1992; 166:244.
  27. McClain DJ, Harrison S, Yeager CL, et al. Immunologic responses to vaccinia vaccines administered by different parenteral routes. J Infect Dis 1997; 175:756.
  28. Sutter G, Moss B. Nonreplicating vaccinia vector efficiently expresses recombinant genes. Proc Natl Acad Sci U S A 1992; 89:10847.
  29. Kennedy JS, Greenberg RN. IMVAMUNE: modified vaccinia Ankara strain as an attenuated smallpox vaccine. Expert Rev Vaccines 2009; 8:13.