Department of Microbiology and Immunology, Jefferson Medical College, Thomas Jefferson University, Philadelphia, PA 19107, USA.
Vaccine. 2010 Dec 10;29(1):130-40. doi: 10.1016/j.vaccine.2010.08.042. Epub 2010 Aug 20.
Dendritic cells (DC) are the most potent antigen presenting cells whose ability to interact with T cells, B cells and NK cells has led to their extensive use in vaccine design. Here, we designed a DC-based HIV-1 vaccine using an attenuated rabies virus vector expressing HIV-1 Gag (RIDC-Gag). To test this, BALB/c mice were immunized with RIDC-Gag, and the primary, secondary as well as humoral immune responses were monitored. Our results indicate that RIDC-Gag stimulated HIV-1 Gag-specific immune responses in mice. When challenged with vaccinia virus (VV) expressing HIV-1 Gag, they elicited a potent Gag-specific recall response characterized by CD8+ T cells expressing multiple cytokines that were capable of specifically lysing Gag-pulsed target cells. Moreover, RIDC-Gag also enhanced CD8+ T cell responses via a homologous prime-boost regimen. These results show that a DC-based vaccine using live RV is immunogenic and a potential candidate for a therapeutic HIV-1 vaccine.
树突状细胞(DC)是最有效的抗原呈递细胞,其与 T 细胞、B 细胞和 NK 细胞相互作用的能力使其在疫苗设计中得到广泛应用。在这里,我们使用表达 HIV-1 Gag 的减毒狂犬病病毒载体(RIDC-Gag)设计了一种基于 DC 的 HIV-1 疫苗。为了验证这一点,用 RIDC-Gag 免疫 BALB/c 小鼠,并监测其初次、二次和体液免疫反应。我们的结果表明,RIDC-Gag 刺激了小鼠的 HIV-1 Gag 特异性免疫反应。当用表达 HIV-1 Gag 的痘苗病毒(VV)进行攻毒时,它们引发了强烈的 Gag 特异性回忆反应,其特征是表达多种细胞因子的 CD8+T 细胞能够特异性杀伤 Gag 脉冲靶细胞。此外,RIDC-Gag 还通过同源初免-加强方案增强了 CD8+T 细胞反应。这些结果表明,使用活 RV 的基于 DC 的疫苗具有免疫原性,是治疗性 HIV-1 疫苗的潜在候选物。