Multigenotype HCV-NS3 recombinant vaccinia viruses as a model for evaluation of cross-genotype immunity induced by HCV vaccines in the mouse

Surrogate infections with HCV-recombinant vaccinia viruses (HCV-rVV) are a standard method to test the efficacy of hepatitis C virus (HCV) vaccine candidates in the mouse model. We established a panel of 16 HCV-rVV expressing the nonstructural protein 3 (NS3) of HCV genotypes 1a, 1b, 2, 3 and 4. Mice immunized with recombinant NS3 protein derived from HCV genotype 1b were challenged with the rVV. rVV-titers decreased up to 54-fold after subtype 1b challenge and up to 8.5-fold after subtype 1a challenge. No change was detected for genotype 2, 3, or 4. Our model is a convenient and reliable tool to analyze the induction of cross-genotype immunity by experimental vaccination of mice.