A plasmid DNA immunogen expressing fifteen protein antigens and complex virus-like particles (VLP+) mimicking naturally occurring HIV.
We describe here a single plasmid DNA immunogen representing the broadest antigen repertoire among HIV vaccine candidates. This pDNA was "ANTIGENeered" for the regulated expression of thirteen complete and two non-functional HIV protein antigens. These proteins self assemble into complex virus-like particles (VLP(+)). Multiple irreversible safety features were introduced by genetic modifications including the complete impairment of integration, reverse transcription, the function of Nef and the 3'LTR. Epitope analysis predicted that the pDNA-derived protein repertoire can potentially present over 3000 T cell epitopes. However, the expressed antigens have different potential to induce HIV-specific CD4(+) and CD8(+) T cells supporting our hypothesis that HIV vaccines should contain all possible regulatory and structural proteins. This immunogen is the active pharmaceutical ingredient of DermaVir, a therapeutic vaccine product candidate that recently successfully completed Phase II clinical trials and meets the safety, immunogenicity and cost requirements of an HIV vaccine.
Genetic Immunity, Berlini utca 47-49, H-1045 Budapest, Hungary.
Eszter
E
Somogyi
Jianqing
J
Xu
Agnes
A
Gudics
József
J
Tóth
Attila L
AL
Kovács
Franco
F
Lori
Julianna
J
Lisziewicz
D016915:AIDS Vaccines / Q000235:genetics / Q000276:immunology*; D002986:Clinical Trials as Topic; D018984:Epitopes, T-Lymphocyte / Q000235:genetics / Q000276:immunology; D015488:HIV Antigens / Q000235:genetics / Q000276:immunology*; D006801:Humans; D008969:Molecular Sequence Data; D010957:Plasmids; D017422:Sequence Analysis, DNA; D019444:Vaccines, DNA / Q000235:genetics / Q000276:immunology*; D014614:Vaccines, Synthetic / Q000235:genetics / Q000276:immunology; D022721:Vaccines, Virosome / Q000235:genetics / Q000276:immunology
D016915:AIDS Vaccines; C501366:DermaVir; D018984:Epitopes, T-Lymphocyte; D015488:HIV Antigens; D019444:Vaccines, DNA; D014614:Vaccines, Synthetic; D022721:Vaccines, Virosome