Yan Jian, Hokey David A, Morrow Matthew P, Corbitt Natasha, Harris Kristina, Harris Drea, Weiner David B
Department of Pathology and Laboratory Medicine, University of Pennsylvania, Philadelphia, PA 19104, USA.
Vaccine. 2009 May 26;27(25-26):3260-6. doi: 10.1016/j.vaccine.2009.01.065. Epub 2009 Feb 5.
Cellular immunity plays an important role in controlling HIV-1 replication. One of the major challenges in developing an HIV-1 DNA vaccine is to generate broader and more potent cellular responses. In this study, we constructed three novel constructs expressing SIVmac antigens Env, Pol and Gag, respectively, with the goal of increasing anti-SIV cellular immunity. The results demonstrate that these constructs can induce strong cellular immune responses in a murine model. Moreover, when applied to cynomolgus macaques, these constructs are not only able to elicit robust IFN-gamma effector responses, but also induce SIV antigen-specific CD8(+) T cells that have high proliferative capacity. These data suggest that such DNA immunogens deserve further examination for their potential to control viral replication.
细胞免疫在控制HIV-1复制中发挥着重要作用。开发HIV-1 DNA疫苗的主要挑战之一是产生更广泛、更有效的细胞反应。在本研究中,我们构建了三种分别表达SIVmac抗原Env、Pol和Gag的新型构建体,目的是增强抗SIV细胞免疫。结果表明,这些构建体可在小鼠模型中诱导强烈的细胞免疫反应。此外,当应用于食蟹猴时,这些构建体不仅能够引发强烈的IFN-γ效应反应,还能诱导具有高增殖能力的SIV抗原特异性CD8(+) T细胞。这些数据表明,此类DNA免疫原在控制病毒复制方面的潜力值得进一步研究。