title: Reverse transcriptase-based DNA vaccines against drug-resistant HIV-1 tested in a mouse model.
abstract: 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.
authors.affiliation: Department of Virology, Swedish Institute for Infectious Disease Control, SE-171 82 Solna, Sweden. maria.isaguliants@smi.ki.se
authors.forename: Maria G
authors.initials: MG
authors.lastname: Isaguliants
authors.forename: Bartek
authors.initials: B
authors.lastname: Zuber
authors.forename: Andreas
authors.initials: A
authors.lastname: Boberg
authors.forename: Dan
authors.initials: D
authors.lastname: Sjöstrand
authors.forename: Sergey V
authors.initials: SV
authors.lastname: Belikov
authors.forename: Erik
authors.initials: E
authors.lastname: Rollman
authors.forename: Anne Kjerrström
authors.initials: AK
authors.lastname: Zuber
authors.forename: Vladimir O
authors.initials: VO
authors.lastname: Rechinsky
authors.forename: Ann-Sofie
authors.initials: AS
authors.lastname: Rytting
authors.forename: Clas F R
authors.initials: CF
authors.lastname: Källander
authors.forename: Jorma
authors.initials: J
authors.lastname: Hinkula
authors.forename: Sergey N
authors.initials: SN
authors.lastname: Kochetkov
authors.forename: Margaret
authors.initials: M
authors.lastname: Liu
authors.forename: Britta
authors.initials: B
authors.lastname: Wahren
mesh_terms: D016915:AIDS Vaccines / Q000235:genetics* / Q000276:immunology*; D000595:Amino Acid Sequence; D000818:Animals; D024882:Drug Resistance, Viral; D004797:Enzyme-Linked Immunosorbent Assay; D000939:Epitopes / Q000276:immunology; D005455:Fluorescent Antibody Technique; D054303:HIV Reverse Transcriptase / Q000235:genetics* / Q000276:immunology*; D015497:HIV-1 / Q000187:drug effects*; D015234:HLA-A Antigens / Q000276:immunology; D007118:Immunoassay; D015151:Immunoblotting; D051379:Mice; D008810:Mice, Inbred C57BL; D008969:Molecular Sequence Data; D009154:Mutation / Q000235:genetics / Q000276:immunology; D009865:Oocytes / Q000378:metabolism; D018894:Reverse Transcriptase Inhibitors / Q000494:pharmacology; D020133:Reverse Transcriptase Polymerase Chain Reaction; D014162:Transfection; D019444:Vaccines, DNA / Q000235:genetics / Q000276:immunology; D014982:Xenopus laevis
chemical_list: D016915:AIDS Vaccines; D000939:Epitopes; D015234:HLA-A Antigens; D018894:Reverse Transcriptase Inhibitors; D019444:Vaccines, DNA; D054303:HIV Reverse Transcriptase