For the development of effective conventional vaccines or DNA vaccines agai
nst viruses, the availability of suitable animal models is an essential pre
requisite. For many recently emerging zoonotic viruses, suitable animal mod
els are still missing. We have established a novel small animal model for D
NA 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 plasm
id DNA encoding the viral envelope proteins G1 and G2. By contrast, vaccina
tion with a plasmid encoding the internal nucleocapsid protein N had little
effect. In an effort to enhance the protective immune response to N we ass
essed the efficacy of vaccination with plasmid DNA encoding N in combinatio
n with a plasmid encoding the cytokine IL-12 as adjuvant. IL-12 enhanced th
e survival of mice following viral challenge, but the effect was independen
t of N indicating the involvement of components of the innate immune system
such as NK cells. Copyright (C) 2001 S. Karger AG, Basel.