Impact of codon usage modification on T cell immunogenicity and longevity of HIV-1 gag-specific DNA vaccines.
In this study, we analyzed the in vitro expression, potency and longevity of immune responses induced in a Balb/c mouse model by a synthetic HIV-1 GAG gene exhibiting a codon usage that was adapted to that of highly expressed mammalian genes (syngag). In contrast to a vector containing the wild-type (wt) GAG gene, the syngag construct enabled highly efficient Gag expression in both human and rodent cell lines in complete absence of Rev and Rev-responsive element. Immunization of Balb/c mice with the wt gag plasmid DNA induced only weak and inconsistent humoral immune responses. Mice vaccinated by syngag but not wt gag developed substantial and highly consistent Gag-specific antibody titers showing a clear T helper 1 polarization even with low doses of DNA. Moreover, vaccinated mice developed a strong Gag-specific cellular immune response, including cytotoxic T cells, which was not observed in wt gag-immunized animals. Both humoral and cellular immunity were efficient and lasted for more than 20 weeks. Furthermore, the induction of the humoral as well as the cellular immune response was independent of the immunization route (intramuscular or subcutaneous). These results clearly show the advantages of codon-optimized genes with respect to the expression and immunogenicity of plasmid DNA constructs, making them promising vaccine candidates for further studies.
Bojak
Alexandra
A
Institute of Medical Microbiology, University of Regensburg, Germany.
Wild
Jens
J
Deml
Ludwig
L
Wagner
Ralf
R
D016915:AIDS Vaccines / Q000008:administration & dosage / Q000276:immunology*; D003062:Codon; D015683:Gene Products, gag / Q000276:immunology*; D015497:HIV-1 / Q000235:genetics / Q000276:immunology*; D006801:Humans; D007273:Injections, Intramuscular; D007279:Injections, Subcutaneous; D013601:T-Lymphocytes / Q000276:immunology*; D014407:Tumor Cells, Cultured; D019444:Vaccines, DNA / Q000008:administration & dosage / Q000276:immunology*
D016915:AIDS Vaccines; D003062:Codon; D015683:Gene Products, gag; D019444:Vaccines, DNA