DNA vaccination against La Crosse virus.
For the development of effective conventional vaccines or DNA vaccines against viruses, the availability of suitable animal models is an essential prerequisite. For many recently emerging zoonotic viruses, suitable animal models are still missing. We have established a novel small animal model for DNA vaccines using mice lacking a functional interferon-alpha/beta receptor (IFNAR-1). IFNAR-1-deficient mice are highly susceptible to many different viruses despite their ability to mount a normal humoral and cellular immune response. Taking advantage of this animal model, we show that mice can be completely protected from lethal challenge with a single injection of plasmid DNA encoding the viral envelope proteins G1 and G2. By contrast, vaccination with a plasmid encoding the internal nucleocapsid protein N had little effect. In an effort to enhance the protective immune response to N we assessed the efficacy of vaccination with plasmid DNA encoding N in combination with a plasmid encoding the cytokine IL-12 as adjuvant. IL-12 enhanced the survival of mice following viral challenge, but the effect was independent of N indicating the involvement of components of the innate immune system such as NK cells.
Institute of Medical Virology, University of Zurich, Switzerland.
J
J
Pavlovic
J
J
Schultz
H P
HP
Hefti
T
T
Schuh
K
K
Mölling
D000818:Animals; D016207:Cytokines / Q000276:immunology; D004195:Disease Models, Animal; D004670:Encephalitis, California / Q000517:prevention & control*; D006801:Humans; D018664:Interleukin-12 / Q000235:genetics / Q000276:immunology; D018062:La Crosse virus / Q000276:immunology*; D008565:Membrane Proteins; D051379:Mice; D010957:Plasmids / Q000276:immunology*; D053633:Receptor, Interferon alpha-beta; D017471:Receptors, Interferon / Q000172:deficiency; D014611:Vaccination; D019444:Vaccines, DNA / Q000276:immunology*; D014759:Viral Envelope Proteins / Q000235:genetics / Q000276:immunology*; D014765:Viral Vaccines / Q000235:genetics / Q000276:immunology*
D016207:Cytokines; C507964:IFNAR1 protein, human; D008565:Membrane Proteins; D017471:Receptors, Interferon; D019444:Vaccines, DNA; D014759:Viral Envelope Proteins; D014765:Viral Vaccines; D053633:Receptor, Interferon alpha-beta; D018664:Interleukin-12