Lori F, Calarota S A, Lisziewicz J
Research Institute for Genetic and Human Therapy, Pavia, Italy.
Curr Med Chem. 2007;14(18):1911-9. doi: 10.2174/092986707781368513.
Highly active antiretroviral treatment (HAART), i.e. the combination of three or more drugs against human immunodeficiency virus type 1 (HIV-1), has greatly improved the clinical outcome of HIV-1-infected individuals. However, HAART is unable to reconstitute HIV-specific immunity and eradicate the virus. Several observations in primate models and in humans support the notion that cell-mediated immunity can control viral replication and slow disease progression. Thus, besides drugs, an immunotherapy that induces long-lasting HIV-specific T-cell responses could play a role in the treatment of HIV/AIDS. To induce such immune responses, DermaVir Patch has been developed. DermaVir consists of an HIV-1 antigen-encoding plasmid DNA that is chemically formulated in a nanoparticle. DermaVir is administered under a patch after a skin preparation that supports the delivery of the nanoparticle to Langerhans cells (LC). Epidermal LC trap and transport the nanomedicine to draining lymph nodes. While in transit, LC mature into dendritic cells (DC), which can efficiently present the DNA-encoded antigens to naïve T-cells for the induction of cellular immunity. Pre-clinical studies and Phase I clinical testing of DermaVir in HIV-1-infected individuals have demonstrated the safety and tolerability of DermaVir Patch. To further modulate cellular immunity, molecular adjuvants might be added into the nanoparticle. DermaVir Patch represents a new nanomedicine platform for immunotherapy of HIV/AIDS. In this review, the antiviral activity of DermaVir-induced cellular immunity is discussed. Furthermore, the action of some cytokines currently being tested as adjuvants are highlighted and the adjuvant effect of cytokine plasmid DNA included in the DermaVir nanoparticle is reviewed.
高效抗逆转录病毒治疗（HAART），即三种或更多种抗1型人类免疫缺陷病毒（HIV-1）药物的联合使用，已极大地改善了HIV-1感染者的临床结局。然而，HAART无法重建HIV特异性免疫并根除病毒。在灵长类动物模型和人类中的一些观察结果支持细胞介导的免疫可以控制病毒复制并减缓疾病进展这一观点。因此，除了药物之外，一种能诱导持久的HIV特异性T细胞反应的免疫疗法可能在HIV/AIDS治疗中发挥作用。为了诱导这种免疫反应，已开发出DermaVir贴片。DermaVir由一种编码HIV-1抗原的质粒DNA组成，该DNA以纳米颗粒的形式进行化学配制。在进行支持纳米颗粒递送至朗格汉斯细胞（LC）的皮肤预处理后，将DermaVir通过贴片给药。表皮LC捕获纳米药物并将其转运至引流淋巴结。在转运过程中，LC成熟为树突状细胞（DC），DC能够有效地将DNA编码的抗原呈递给幼稚T细胞以诱导细胞免疫。DermaVir在HIV-1感染者中的临床前研究和I期临床试验已证明DermaVir贴片的安全性和耐受性。为了进一步调节细胞免疫，可将分子佐剂添加到纳米颗粒中。DermaVir贴片代表了一种用于HIV/AIDS免疫治疗的新型纳米药物平台。在这篇综述中，讨论了DermaVir诱导的细胞免疫的抗病毒活性。此外，还强调了目前作为佐剂进行测试的一些细胞因子的作用，并综述了DermaVir纳米颗粒中包含的细胞因子质粒DNA的佐剂效应。
