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.
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 modifiedVACV 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:ECTVinfection in mice models the course of humansmallpox. 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: M S Keckler; D S Carroll; N F Gallardo-Romero; R R Lash; J S Salzer; S L Weiss; N Patel; C J Clemmons; S K Smith; C L Hutson; K L Karem; I K Damon Journal: J Virol Date: 2011-06-01 Impact factor: 5.103
Authors: Bertram L Jacobs; Jeffrey O Langland; Karen V Kibler; Karen L Denzler; Stacy D White; Susan A Holechek; Shukmei Wong; Trung Huynh; Carole R Baskin Journal: Antiviral Res Date: 2009-06-26 Impact factor: 5.970
Authors: Georg Pauli; Johannes Blümel; Reinhard Burger; Christian Drosten; Albrecht Gröner; Lutz Gürtler; Margarethe Heiden; Martin Hildebrandt; Bernd Jansen; Thomas Montag-Lessing; Ruth Offergeld; Rainer Seitz; Uwe Schlenkrich; Volkmar Schottstedt; Johanna Strobel; Hannelore Willkommen; Carl-Heinz Wirsing von König Journal: Transfus Med Hemother Date: 2010-11-17 Impact factor: 3.747