Vaccine and Infectious Disease Division, Fred Hutchinson Cancer Research Center, Seattle, M2-C200, WA, USA; Department of Global Health, University of Washington, Seattle, WA, USA.
Centre Hospitalier Universitaire Vaudois, Rue du Bugnon 46, BH10-527, CH-1011 Lausanne, Switzerland.
EBioMedicine. 2017 Oct;24:195-204. doi: 10.1016/j.ebiom.2017.09.028. Epub 2017 Sep 22.
In a placebo-controlled trial of the peptide-based therapeutic HIV-1 p24 vaccine candidate Vacc-4x, participants on combination antiretroviral therapy (cART) received six immunizations over 18weeks, followed by analytical treatment interruption (ATI) between weeks 28 and 52. Cell-mediated immune responses were investigated as predictors of Vacc-4x effect (VE) on viral load (VL) and CD4 count during ATI.
All analyses of week 28 responses and fold-changes relative to baseline considered per-protocol participants (Vacc-4x:placebo=72:32) resuming cART after week 40. Linear regression models with interaction tests were used. VE was estimated as the Vacc-4x-placebo difference in log-transformed VL (VE) or CD4 count (VE).
A lower fold-change of CD4+ T-cell proliferation was associated with VE at week 48 (p=0.036, multiplicity adjusted q=0.036) and week 52 (p=0.040, q=0.080). A higher fold-change of IFN-γ in proliferation supernatants was associated with VE at week 44 (p=0.047, q=0.07). A higher fold-change of TNF-α was associated with VE at week 44 (p=0.045, q=0.070), week 48 (p=0.028, q=0.070), and week 52 (p=0.037, q=0.074). A higher fold-change of IL-6 was associated with VE at week 48 (p=0.017, q=0.036). TNF-α levels (>median) were associated with VE at week 48 (p=0.009, q=0.009).
These exploratory analyses highlight the potential value of investigating biomarkers in T-cell proliferation supernatants for VE in clinical studies.
在一项针对基于肽的治疗性 HIV-1 p24 疫苗候选物 Vacc-4x 的安慰剂对照试验中，接受联合抗逆转录病毒治疗 (cART) 的参与者在 18 周内接受了 6 次免疫接种，然后在第 28 周至第 52 周进行分析性治疗中断 (ATI)。细胞介导的免疫反应被研究作为预测 Vacc-4x 对病毒载量 (VL) 和 CD4 计数的影响 (VE) 在 ATI 期间。
所有对第 28 周反应的分析和相对于基线的倍数变化都考虑了在第 40 周后恢复 cART 的方案参与者（Vacc-4x：安慰剂=72：32）。使用带有交互测试的线性回归模型。VE 被估计为 Vacc-4x-安慰剂在对数转换的 VL（VE）或 CD4 计数（VE）中的差异。
CD4+T 细胞增殖的较低倍数变化与第 48 周（p=0.036，多重调整 q=0.036）和第 52 周（p=0.040，q=0.080）的 VE 相关。增殖上清液中 IFN-γ 的更高倍数变化与第 44 周的 VE 相关（p=0.047，q=0.07）。TNF-α 的更高倍数变化与第 44 周（p=0.045，q=0.070）、第 48 周（p=0.028，q=0.070）和第 52 周（p=0.037，q=0.074）的 VE 相关。IL-6 的更高倍数变化与第 48 周的 VE 相关（p=0.017，q=0.036）。TNF-α 水平（>中位数）与第 48 周的 VE 相关（p=0.009，q=0.009）。
这些探索性分析强调了在临床试验中研究 T 细胞增殖上清液中的生物标志物对 VE 的潜在价值。
