Recombinant RNA based on the Semliki Forest virus (SFV) replicon was u
sed to express the nucleoprotein of influenza virus in mice. Two strat
egies were employed to deliver the RNA. In the first, recombinant RNA
was packaged into infectious suicide SFV particles which were used dir
ectly for immunization. The second approach involved injection of in v
itro-synthesized RNA directly into the quadriceps muscle. Both approac
hes resulted in the generation of humoral responses with high antibody
titres. Immunization with suicide particles showed that a strong, cla
ss I-restricted cytotoxic T-cell response can be obtained using only 1
00 infectious units. We conclude that the self-replicative recombinant
SFV RNA may be quite useful as a nucleic acid vaccine.