Reverse transcriptase-based DNA vaccines against drug-resistant HIV-1 tested in a mouse model.

Drug resistance is becoming a problem in the treatment of the human immunodeficiency virus type one (HIV-1). To obtain therapeutic DNA vaccines that would target multiple drug-resistance (DR) mutations, we cloned genes for DR HIV-1 reverse transcriptase (RT) and codon-optimized synthetic genes encoding clusters of human CTL epitopes located at the sites of DR-mutations (RT minigenes) and antibody and CTL-epitope tags. Expression of RT genes/minigenes in eukaryotic cells was confirmed by Western blotting and immunofluoresence staining with RT- or tag-specific antibodies. Immunization of mice with DR-RT gene induced no RT-specific antibodies. Immunization of HLA-A(*)0201-transgenic mice with RT minigenes induced RT-specific cellular responses detected by interferon-gamma secretion. This documents first steps in creating therapeutic vaccine against drug-resistant HIV strains.