title: Pre-clinical efficacy and safety of experimental vaccines based on non-replicating vaccinia vectors against yellow fever.
abstract: BACKGROUND
  Currently existing yellow fever (YF) vaccines are based on the live attenuated yellow fever virus 17D strain (YFV-17D). Although, a good safety profile was historically attributed to the 17D vaccine, serious adverse events have been reported, making the development of a safer, more modern vaccine desirable.
  
  
  RESULTS
  A gene encoding the precursor of the membrane and envelope (prME) protein of the YFV-17D strain was inserted into the non-replicating modified vaccinia virus Ankara and into the D4R-defective vaccinia virus. Candidate vaccines based on the recombinant vaccinia viruses were assessed for immunogenicity and protection in a mouse model and compared to the commercial YFV-17D vaccine. The recombinant live vaccines induced γ-interferon-secreting CD4- and functionally active CD8-T cells, and conferred full protection against lethal challenge already after a single low immunization dose of 10(5) TCID(50). Surprisingly, pre-existing immunity against wild-type vaccinia virus did not negatively influence protection. Unlike the classical 17D vaccine, the vaccinia virus-based vaccines did not cause mortality following intracerebral administration in mice, demonstrating better safety profiles.
  
  
  CONCLUSIONS
  The non-replicating recombinant YF candidate live vaccines induced a broad immune response after single dose administration, were effective even in the presence of a pre-existing immunity against vaccinia virus and demonstrated an excellent safety profile in mice.
authors.affiliation: Department of Virology, Baxter Bioscience, Biomedical Research Center, Orth/Donau, Austria.
authors.forename: Birgit
authors.initials: B
authors.lastname: Schäfer
authors.forename: Georg W
authors.initials: GW
authors.lastname: Holzer
authors.forename: Alexandra
authors.initials: A
authors.lastname: Joachimsthaler
authors.forename: Sogue
authors.initials: S
authors.lastname: Coulibaly
authors.forename: Michael
authors.initials: M
authors.lastname: Schwendinger
authors.forename: Brian A
authors.initials: BA
authors.lastname: Crowe
authors.forename: Thomas R
authors.initials: TR
authors.lastname: Kreil
authors.forename: P Noel
authors.initials: PN
authors.lastname: Barrett
authors.forename: Falko G
authors.initials: FG
authors.lastname: Falkner
mesh_terms: D000818:Animals; D015496:CD4-Positive T-Lymphocytes / Q000821:virology; D018414:CD8-Positive T-Lymphocytes / Q000821:virology; D002522:Chlorocebus aethiops; D006367:HeLa Cells; D006801:Humans; D007107:Immune System; D051379:Mice; D008807:Mice, Inbred BALB C; D010957:Plasmids / Q000378:metabolism; D014613:Vaccines, Attenuated / Q000627:therapeutic use; D014616:Vaccinia virus / Q000378:metabolism*; D014709:Vero Cells; D014759:Viral Envelope Proteins / Q000737:chemistry; D014765:Viral Vaccines / Q000627:therapeutic use*; D015004:Yellow Fever / Q000517:prevention & control*; D022341:Yellow Fever Vaccine / Q000627:therapeutic use*
chemical_list: D014613:Vaccines, Attenuated; D014759:Viral Envelope Proteins; D014765:Viral Vaccines; D022341:Yellow Fever Vaccine