Vaccinia virus vaccines: past, present and future

Antiviral Res. 2009 Oct;84(1):1-13. doi: 10.1016/j.antiviral.2009.06.006. Epub 2009 Jun 26.


Vaccinia virus (VACV) has been used more extensively for human immunization than any other vaccine. For almost two centuries, VACV was employed to provide cross-protection against variola virus, the causative agent of smallpox, until the disease was eradicated in the late 1970s. Since that time, continued research on VACV has produced a number of modified vaccines with improved safety profiles. Attenuation has been achieved through several strategies, including sequential passage in an alternative host, deletion of specific genes or genetic engineering of viral genes encoding immunomodulatory proteins. Some highly attenuated third- and fourth-generation VACV vaccines are now being considered for stockpiling against a possible re-introduction of smallpox through bioterrorism. Researchers have also taken advantage of the ability of the VACV genome to accommodate additional genetic material to produce novel vaccines against a wide variety of infectious agents, including a recombinant VACV encoding the rabies virus glycoprotein that is administered orally to wild animals. This review provides an in-depth examination of these successive generations of VACV vaccines, focusing on how the understanding of poxviral replication and viral gene function permits the deliberate modification of VACV immunogenicity and virulence.

Publication types

  • Historical Article
  • Review

MeSH terms

  • Animals
  • Genetic Engineering
  • History, 20th Century
  • History, 21st Century
  • Humans
  • Smallpox Vaccine / genetics
  • Smallpox Vaccine / history*
  • Smallpox Vaccine / immunology
  • Vaccinia / immunology
  • Vaccinia / prevention & control*
  • Vaccinia / virology
  • Vaccinia virus / genetics*
  • Vaccinia virus / immunology*
  • Vaccinia virus / pathogenicity
  • Vaccinia virus / physiology
  • Virulence


  • Smallpox Vaccine