Two HCV vaccines based on adeno-associated virus vectors elicited durable and effective immune responses in mice / 病毒学报

ABSTRACT

Recombinant adeno-associated viruses (rAAV) vectors have been shown to mediate long-term transgene expression in mice and nonhuman primates. We have adapted viral vector system based on two rAAV vectors, namely rAAV1 and rAAV2. We have generated rAAV vectors expressing the envelope glycoprotein (E1 and E2) derived from Chinese HCV patient (genotype 1b) and used these to immunize BALB/c mice. We detected the total antibody titer by IFA and neutralizing antibody (nAb) using in vitro HCV neutralizing assays based on HCV pseudotyped particles. Furthermore, IFN-gamma ELISpot assay was used to assess the T cellular response against HCV at 12 weeks after rAAV1-E1E2 immunization. We also analyzed HCV envelope glycoprotein expression in muscle of rAAV1-E1E2 immunized mice. Our data showed (i) rAAV1 directed long-term expression of HCV genes in mice; (ii) immunized intramuscularly with a single dose of rAAV elicited durable and effective immune responses in mice; and (iii) Moreover, rAAV1-E1E2 induced higher total antibody and nAb titers than rAAV2-E1E2 did. These data suggest that rAAV1 vectors could stimulate robust, durable, and effective immune responses against HCV.