Human immunodeficiency virus type-1 (HIV-1)-specific dendritic cell (DC)
vaccines have been used in clinical trials. However, they have been found to only induce some degree of immune responses in these studies. We previously demonstrated that the HIV-1 Gag-specific Gag-Texo
vaccine stimulated Gag-specific effector CD8(+) cytotoxic T lymphocyte (CTL) responses, leading to completely protective, but very limited, therapeutic immunity. In this study, we constructed a recombinant adenoviral vector, adenovirus (AdV)4-1BBL, which expressed mouse
4-1BB ligand (4-1BBL), and generated transgenic 4-1BBL-engineered OVA-Texo/4-1BBL and Gag-Texo/4-1BBL
vaccines by transfecting
ovalbumin (OVA)-Texo and Gag-Texo cells with AdV4-1BBL, respectively. We demonstrate that the OVA-specific OVA-Texo/4-1BBL
vaccine stimulates more efficient OVA-specific CTL responses (3.26%) compared to OVA-Texo-activated responses (1.98%) in wild-type C57BL/6 mice and the control OVA-Texo/Null
vaccine without transgenic 4-1BBL expression, leading to enhanced therapeutic immunity against 6-day established OVA-expressing
B16 melanoma BL6-10OVA cells. OVA-Texo/4-1BBL-stimulated CTLs, which have a CD44(+)CD62L(high) IL-7R(+) phenotype, are likely memory CTL precursors, demonstrating prolonged survival and enhanced differentiation into memory CTLs with functional recall responses and long-term immunity against BL6-10OVA
melanoma. In addition, we demonstrate that OVA-Texo/4-1BBL-stimulated CTLs up- and downregulate the expression of anti-apoptosis (Bcl2l10, Naip1, Nol3, Pak7 and Tnfrsf11b) and pro-apoptosis (Casp12, Trp63 and Trp73) genes, respectively, by RT(2) Profiler PCR array analysis. Importantly, the Gag-specific Gag-Texo/4-1BBL
vaccine also stimulates more efficient Gag-specific therapeutic and long-term immunity against HLA-A2/Gag-expressing
B16 melanoma BL6-10Gag/A2 cells than the control Gag-Texo/Null
vaccine in transgenic
HLA-A2 mice. Taken together, our novel Gag-Texo/4-1BBL
vaccine, which is capable of stimulating potent Gag-specific therapeutic and long-term immunity, may represent a new immunotherapeutic
vaccine for controlling HIV-1
infection.