title: Postexposure immunization with modified vaccinia virus Ankara or conventional Lister vaccine provides solid protection in a murine model of human smallpox.
abstract: BACKGROUND
  Decades after the cessation of smallpox vaccination, the potential of the deliberate release of pathogenic orthopoxviruses has forced a reconsideration of using these extremely efficient human vaccines. Scenarios of sudden biothreats have prompted demand for rapidly protective vaccination. However, the feasibility of short-term vaccination (i.e., vaccination shortly before exposure) with vaccinia virus (VACV) is uncertain.
  
  
  METHODS
  We tested the rapid protective capacity of vaccines based on VACV strain Lister (VACV-Lister) and on modified VACV Ankara (MVA) in different mouse models, comparing lethal infections with VACV strain Western Reserve (VACV-WR) or ectromelia virus (ECTV).
  
  
  RESULTS
  In contrast to VACV-WR challenge, we found extended incubation periods after ECTV challenge, allowing successful therapeutic immunization with VACV-Lister and MVA when applied 2-3 days after exposure. Rapid protection from respiratory tract ECTV infection was significantly affected by vaccine dose and was associated with occurrence of poxvirus-specific antibodies. Vaccinations in type I interferon receptor-deficient mice were protective, whereas recombination activating gene 1-deficient mice lacking mature T and B cells failed to mount immunity after short-term vaccination, confirming an essential role of adaptive immune responses.
  
  
  CONCLUSIONS
  ECTV infection in mice models the course of human smallpox. Our data provide evidence to substantiate historical data on the usefulness of postexposure vaccination with conventional VACV and the new candidate MVA to protect against fatal orthopoxvirus infections.
authors.affiliation: Israel Institute for Biological Research, Ness-Ziona, Israel.
authors.forename: Nir
authors.initials: N
authors.lastname: Paran
authors.forename: Yasemin
authors.initials: Y
authors.lastname: Suezer
authors.forename: Shlomo
authors.initials: S
authors.lastname: Lustig
authors.forename: Tomer
authors.initials: T
authors.lastname: Israely
authors.forename: Astrid
authors.initials: A
authors.lastname: Schwantes
authors.forename: Sharon
authors.initials: S
authors.lastname: Melamed
authors.forename: Lior
authors.initials: L
authors.lastname: Katz
authors.forename: Thomas
authors.initials: T
authors.lastname: Preuss
authors.forename: Kay-Martin
authors.initials: KM
authors.lastname: Hanschmann
authors.forename: Ulrich
authors.initials: U
authors.lastname: Kalinke
authors.forename: Noam
authors.initials: N
authors.lastname: Erez
authors.forename: Reuven
authors.initials: R
authors.lastname: Levin
authors.forename: Baruch
authors.initials: B
authors.lastname: Velan
authors.forename: Johannes
authors.initials: J
authors.lastname: Löwer
authors.forename: Avigdor
authors.initials: A
authors.lastname: Shafferman
authors.forename: Gerd
authors.initials: G
authors.lastname: Sutter
mesh_terms: D000818:Animals; D002460:Cell Line; D002522:Chlorocebus aethiops; D006224:Cricetinae; D004195:Disease Models, Animal; D018450:Disease Progression; D004781:Environmental Exposure; D006367:HeLa Cells; D006801:Humans; D051379:Mice; D012141:Respiratory Tract Infections / Q000276:immunology / Q000821:virology; D012899:Smallpox / Q000276:immunology* / Q000503:physiopathology / Q000517:prevention & control; D012900:Smallpox Vaccine / Q000235:genetics / Q000276:immunology / Q000627:therapeutic use*; D014616:Vaccinia virus / Q000145:classification / Q000276:immunology*; D014709:Vero Cells; D019562:Viral Load
chemical_list: D012900:Smallpox Vaccine