Center for Vaccinology, Ghent University and Hospital, Ghent, Belgium.
Vaccine. 2013 Aug 12;31(36):3739-46. doi: 10.1016/j.vaccine.2013.05.021. Epub 2013 May 21.
A recombinant fusion protein (F4) consisting of HIV-1 p17, p24, reverse transcriptase (RT) and Nef, adjuvanted with AS01, induced strong and broad CD4(+) T cell responses in healthy volunteers. Here we compare these vaccine-induced CD4(+) T cell responses with the ones induced by natural infection in patients with varying disease courses. Thirty-eight HIV-infected, antiretroviral treatment-naïve subjects were classified into four categories: 8 long-term non-progressors (infection ≥7 years; CD4(+) T cells ≥500/μL), 10 recently infected individuals (infection ≤2 years; CD4(+) T cells ≥500/μL), 10 typical early progressors (CD4(+) T cells ≤350/μL), and 10 viral controllers (plasma HIV-1 RNA <1000copies/mL). Peripheral blood mononuclear cells were stimulated in vitro with p17, p24, RT and Nef peptide pools and analyzed by flow cytometry for expression of IL-2, IFN-γ, TNF-α and CD40L. CD4(+) T cell responses were compared to those measured with the same method in 50 HIV-uninfected subjects immunized with the F4/AS01 candidate vaccine (NCT00434512). After in vitro stimulation with p17, p24 and RT antigen viral controllers had significantly more CD4(+) T cells co-expressing IL-2, IFN-γ and TNF-α than other HIV patient categories. The magnitude and quality of these responses in viral controllers were comparable to those observed in F4/AS01 vaccine recipients. In contrast with viral controllers, triple cytokine producing CD4(+) T cells in vaccinees also expressed CD40L. Subjects who spontaneously control an HIV infection display polyfunctional CD4(+) T cell responses to p17, p24, RT and Nef, with similar magnitude and qualities as those induced in healthy volunteers by an adjuvanted HIV candidate vaccine (F4/AS01).
一种由 HIV-1 p17、p24、逆转录酶（RT）和 Nef 组成的重组融合蛋白（F4），与 AS01 佐剂联合使用，在健康志愿者中诱导出强烈而广泛的 CD4(+) T 细胞反应。在这里，我们将这些疫苗诱导的 CD4(+) T 细胞反应与不同疾病进程的患者中自然感染诱导的反应进行比较。38 名未经抗逆转录病毒治疗的 HIV 感染患者被分为四组：8 名长期非进展者（感染≥7 年；CD4(+) T 细胞≥500/μL），10 名新近感染者（感染≤2 年；CD4(+) T 细胞≥500/μL），10 名典型早期进展者（CD4(+) T 细胞≤350/μL）和 10 名病毒控制器（血浆 HIV-1 RNA<1000 拷贝/mL）。外周血单核细胞在体外用 p17、p24、RT 和 Nef 肽池刺激，并通过流式细胞术分析 IL-2、IFN-γ、TNF-α 和 CD40L 的表达。将 CD4(+) T 细胞反应与用相同方法测量的 50 名未感染 HIV 的 F4/AS01 候选疫苗接种者的反应进行比较（NCT00434512）。在体外用 p17、p24 和 RT 抗原刺激后，病毒控制器的 CD4(+) T 细胞共表达 IL-2、IFN-γ 和 TNF-α 的数量明显多于其他 HIV 患者组。病毒控制器中这些反应的幅度和质量与 F4/AS01 疫苗接种者观察到的反应相当。与病毒控制器不同的是，疫苗接种者中产生三因子的 CD4(+) T 细胞也表达 CD40L。自发控制 HIV 感染的受试者对 p17、p24、RT 和 Nef 产生多效性 CD4(+) T 细胞反应，其幅度和质量与健康志愿者用佐剂 HIV 候选疫苗（F4/AS01）诱导的反应相似。
