Calarota Sandra A, Dai Anlan, Trocio Jeffrey N, Weiner David B, Lori Franco, Lisziewicz Julianna
Research Institute for Genetic and Human Therapy (RIGHT), 27100 Pavia, Italy.
Vaccine. 2008 Sep 19;26(40):5188-95. doi: 10.1016/j.vaccine.2008.03.067. Epub 2008 Apr 14.
IL-7 and IL-15 are key cytokines involved in the generation and maintenance of memory CD8+ T-cells. We evaluated these cytokines as molecular adjuvants for topical HIV-1 DermaVir vaccine. We found that mice receiving DermaVir formulated with HIV-1 Gag plasmid in the presence of IL-7- or IL-15-encoding plasmid significantly enhanced Gag-specific central memory T-cells, as measured by a peptide-based cultured IFN-gamma ELISPOT. Additionally, IL-15 significantly improved DermaVir-induced Gag-specific effector memory CD8+ T-cell responses, measured by standard IFN-gamma ELISPOT. In a DermaVir prime/vaccinia vector boost regimen, the inclusion of IL-15 together with DermaVir significantly improved Gag-specific effector memory T-cell responses. Our study demonstrates that IL-15 is more potent than IL-7 in enhancing HIV-1-specific central memory T-cells induced by topical DermaVir. IL-15 adjuvanted DermaVir might be an alternative prime in a prophylactic vaccine regimen.
白细胞介素-7(IL-7)和白细胞介素-15(IL-15)是参与记忆性CD8 + T细胞产生和维持的关键细胞因子。我们评估了这些细胞因子作为局部应用的HIV-1 DermaVir疫苗的分子佐剂的效果。我们发现,在存在编码IL-7或IL-15的质粒的情况下,接受用HIV-1 Gag质粒配制的DermaVir的小鼠,通过基于肽的培养的γ干扰素酶联免疫斑点法(IFN-γ ELISPOT)检测,其Gag特异性中枢记忆T细胞显著增加。此外,通过标准的γ干扰素酶联免疫斑点法检测,IL-15显著改善了DermaVir诱导的Gag特异性效应记忆CD8 + T细胞反应。在DermaVir初免/痘苗病毒载体加强免疫方案中,将IL-15与DermaVir一起使用可显著改善Gag特异性效应记忆T细胞反应。我们的研究表明,在增强局部应用DermaVir诱导的HIV-1特异性中枢记忆T细胞方面,IL-15比IL-7更有效。IL-15佐剂化的DermaVir可能是预防性疫苗方案中的一种替代初免制剂。