title: A truncated plasmid-encoded HIV-1 reverse transcriptase displays strong immunogenicity.
abstract: Besides being an important target in the antiretroviral therapy against the human immunodeficiency virus type 1 (HIV-1), the HIV-1 reverse transcriptase (RT) enzyme has potential as a vaccine antigen. In this study, we explored the ability of plasmid-encoded RT to induce cell-mediated immune responses. The strategy for increasing the immunogenicity of the protein was to delete non- or low-immunogenic parts in order to focus the immune responses to known immunogenic regions. Expression and immunogenicity of the truncated RT was compared to a clinically evaluated full-length RT construct, and the truncated RT displayed enhanced in vitro expression and cell-mediated immune responses in BALB/c and HLA-A0201 transgenic C57BL/6 mice. The strong immune responses were retained also when the truncated RT was delivered as a part of a multigene HIV-1 vaccine. Linking the RT gene to a highly expressed HIV-1 protease gene did not increase the immunogenicity of RT. This optimization strategy could be used to enhance the immunogenicity of other RT-encoding DNA vaccines.
authors.affiliation: Department of Microbiology, Tumor and Cell Biology, Karolinska Institutet, Stockholm, Sweden. david.hallengard@ki.se
authors.forename: David
authors.initials: D
authors.lastname: Hallengärd
authors.forename: Britta
authors.initials: B
authors.lastname: Wahren
authors.forename: Andreas
authors.initials: A
authors.lastname: Bråve
mesh_terms: D016915:AIDS Vaccines / Q000008:administration & dosage / Q000235:genetics / Q000276:immunology*; D000595:Amino Acid Sequence; D000818:Animals; D016207:Cytokines / Q000378:metabolism; D005260:Female; D054303:HIV Reverse Transcriptase / Q000235:genetics / Q000276:immunology*; D015497:HIV-1 / Q000235:genetics / Q000276:immunology*; D015789:HLA-A2 Antigen / Q000235:genetics; D006801:Humans; D007963:Leukocytes, Mononuclear / Q000276:immunology; D051379:Mice; D008807:Mice, Inbred BALB C; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D008969:Molecular Sequence Data; D010957:Plasmids; D017384:Sequence Deletion; D013154:Spleen / Q000276:immunology; D019444:Vaccines, DNA / Q000008:administration & dosage / Q000235:genetics / Q000276:immunology*
chemical_list: D016915:AIDS Vaccines; D016207:Cytokines; C435939:HLA-A*02:01 antigen; D015789:HLA-A2 Antigen; D019444:Vaccines, DNA; C514824:reverse transcriptase, Human immunodeficiency virus 1; D054303:HIV Reverse Transcriptase