Rabies virus-based vectors expressing human immunodeficiency virus type 1 (HIV-1) envelope protein induce a strong, cross-reactive cytotoxic T-lymphocyte response against envelope proteins from different HIV-1 isolates

Novel viral vectors that are able to induce both strong and long-lasting im mune responses may be required as effective vaccines for human immunodefici ency virus type I (HIV-1) infection. Our previous experiments with a replic ation-competent vaccine strain-based rabies virus (RV) expressing HIV-1 env elope protein from a laboratory-adapted HIV-1 strain (NL4-3) and a primary HIV-1 isolate (89.6) shelved that RV-based vectors are excellent for B-cell priming. Here we report that cytotoxic T-Lymphocyte (CTL) responses agains t HIV-I gp160 are induced by recombinant RVs. Our results indicated that a single inoculation of mice with an RV expressing HIV-1 gp160 induced a soli d and long-lasting memory CTL response specific for HIV-1 envelope protein. Moreover, CTLs from immunized mice were not restricted to the homologous H IV-I envelope protein and were able to cross-kill target cells expressing H IV-1 gp160 from heterologous HIV-1 strains. These studies further suggest p romise for RV-based vectors to elicit a persistent immune response against HIV-1 and their potential utility as efficacious anti-HIV-1 vaccines.