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.
Isaguliants
Maria G
MG
Department of Virology, Swedish Institute for Infectious Disease Control, SE-171 82 Solna, Sweden. maria.isaguliants@smi.ki.se
Zuber
Bartek
B
Boberg
Andreas
A
Sjöstrand
Dan
D
Belikov
Sergey V
SV
Rollman
Erik
E
Zuber
Anne Kjerrström
AK
Rechinsky
Vladimir O
VO
Rytting
Ann-Sofie
AS
Källander
Clas F R
CF
Hinkula
Jorma
J
Kochetkov
Sergey N
SN
Liu
Margaret
M
Wahren
Britta
B
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
D016915:AIDS Vaccines; D000939:Epitopes; D015234:HLA-A Antigens; D018894:Reverse Transcriptase Inhibitors; D019444:Vaccines, DNA; D054303:HIV Reverse Transcriptase