%0 Journal Article
%T The Tat Protein Enhances CTL Responses and Therapeutic Immunity of Gag-Specific Exosome-Targeted T Cell-Based Gag/Tat-Texo Vaccine in Transgenic HLA-A2 Mice
%A Aizhang Xu
%A Jie Wu
%A Yufeng Xie
%A Rajni Chibbar
%A Andrew Fleywald
%A Jim Xiang
%J World Journal of Vaccines
%P 11-25
%@ 2160-5823
%D 2017
%I Scientific Research Publishing
%R 10.4236/wjv.2017.72002
%X Human immunodeficiency virus type-1 (HIV-1) chronic infection causes millions of deaths each year. We previously developed a novel HIV-1 Gag-spe cific exosome (EXO)-targeted T cell-based vaccine (Gag-Texo) using ConAstimulated polyclonal CD8<sup>+</sup>T (ConA-T) cells armed with Gag-specific dendritic cell (DC)-released EXOs, and showed that Gag-Texo stimulated more efficient cytotoxic T lymphocyte (CTL) responses than DCs. Tat HIV-1 early regulatory protein possesses immunomodulatory and adjuvant properties. To enhance Gag-Texo immunogenicity, we generated Tat-engineered OVA/Tat Texo and Gag/Tat-Texo vaccines using ConA-T cells armed with EXOs release by DCs infected with recombinant OVA/Tat- and Gag/Tat-expressing adenoviruses (AdV<sub>OVA/Tat</sub> and AdV<sub>Gag/Tat</sub>). We then assessed vaccination-stimulated CTL responses in naive mice, and therapeutic immunity in transgenic HLA-A2 mice bearing Gag/HLA-A2-expressing BL6-10<sub>OVA/A2</sub> melanoma lung metastases. We demonstrate that the OVA/Tat-Texo vaccine enhances functional OVA-specific CTL responses, compared to the OVA-Texo vaccine, and broadens CTL responses recognizing the cryptic OVA epitope in C57BL/6 mice. Furthermore, we determine that the Gag/Tat-Texo not only stimulates more efficient CTL responses than Gag-Texo, but also induces enhanced therapeutic immunity. We show that, 30% of Gag/Tat-Texo-immunized mice are free of tumor lung-metastases, compared to all Gag-Texo-immunized mice displaying lung-metastasis. In addition, the average number of tumor lung metastases colonies (32/lung) in the Gag/Tat-Texo-immunized mice was also significantly lower than that (78/lung) observed in Gag-Texo-immunized mice. Taken together, this indicates that HIV-1 Gag/Tat-Texo capable of stimulating enhanced Gag-specific CTL responses and therapeutic immunity may become a new immunotherapeutic vaccine candidate for controlling virus in HIV-1 patients.
%K Tat
%K T-Cell Vaccine
%K Gag
%K Exosome
%K CTL
%K Therapeutic Immunity
%K Transgenic HLA-A2 Mice
%U http://www.scirp.org/journal/PaperInformation.aspx?PaperID=76623