具有Viread的新型疫苗诱导慢性HBV中的T细胞免疫应答

StephenW

Novel vaccine with Viread induces T cell immune response in chronic HBV

Boni C, et al. Gastroenterol. 2019;doi:10.1053/j.gastro.2019.03.044.
May 31, 2019

Researchers found that treatment with a combination of Viread and GS-4774, a yeast-based therapeutic vaccine, increased hepatitis B-specific T cell immune response in untreated patients with chronic hepatitis B.

"HBV-specific T cells are substantially exhausted in untreated patients with chronic hepatitis B (CHB): reconstitution of their antiviral function represents a major goal of HBV immune therapies," Carolina Boni, MD, from the University of Parma in Italy, and colleagues "Therapeutic compounds designed to restore an effective HBV-specific T-cell response represent promising tools for improving the rate of HBsAg loss and seroconversion in subjects with CHB compared with what is currently achievable with [nucleo(s)tide] alone."


Boni and colleagues randomly assigned 195 patients to receive Viread (tenofovir disoproxil fumarate or TDF, Gilead Sciences) with GS-4774 (n = 168) or TDF alone (n = 27). While GS-4774 was originally engineered and evaluated to affect HBV Surface antigen levels, the researchers found no significant differences between the two groups in HBsAg decline from baseline.

However, patients treated with the GS-4774 vaccine had significantly increased production of interferon gamma (IFNG), tumor necrosis factor (TNF) and interleukin 2 (IL2) by HBV-specific cytotoxic T cells at week 24 and week 48 compared with baseline. Cancer treated with TDF alone showed no significant changes in immune response.

"Evolution of T-cell responses in patients treated with combined GS-4774 and tenofovir is well illustrated by hierarchical-clustering analysis of all data derived from all time points of therapy and from the reference acute hepatitis B control group for the definition of an efficient Immune response able to control infection spontaneously," the scientist wrote.

GS-4774 was generally well-tolerated. The most common treatment-emergent adverse events associated with injection site included pain, erythema and swelling, while other common events included fatigue and headache.

" ""Future combination therapies including vaccines should consider the sequential administration of drugs able to improve T-cell responsiveness to antigen stimulation by lowering the antigen load, such as, for example, silencing RNA compounds or capsid assembly inhibitors, or by inhibiting immune checkpoints or modulating T-cell metabolism, followed by T- and B-cell boosting through vaccination,” Boni and colleagues concluded. – by Talitha Bennett

Disclosure: The authors report no relevant financial disclosures.

StephenW

具有Viread的新型疫苗诱导慢性HBV中的T细胞免疫应答

Boni C，et al。 Gastroenterol。 2019; DOI：10.1053 / j.gastro.2019.03.044。
2019年5月31日

研究人员发现，使用Viread和GS-4774（一种基于酵母的治疗性疫苗）联合治疗可增加未治疗慢性乙型肝炎患者的乙型肝炎特异性T细胞免疫应答。

“HBV特异性T细胞在未经治疗的慢性乙型肝炎患者（CHB）中基本耗尽：其抗病毒功能的重建是HBV免疫治疗的主要目标，”来自意大利帕尔马大学的Carolina Boni博士及其同事“旨在恢复有效的HBV特异性T细胞反应的治疗化合物代表了有希望的工具，用于改善CHB受试者的HBsAg丢失率和血清转换率，而单独使用[核潮]目前可以实现这一目标。”


Boni及其同事随机分配了195名患者接受Viread（替诺福韦地索普西富马酸盐或TDF，Gilead Sciences），其中GS-4774（n = 168）或单独使用TDF（n = 27）。尽管GS-4774最初被设计和评估以影响HBV表面抗原水平，但研究人员发现两组HBsAg与基线相比没有显着差异。

然而，与基线相比，在第24周和第48周，用GS-4774疫苗治疗的患者通过HBV特异性细胞毒性T细胞显着增加干扰素γ（IFNG），肿瘤坏死因子（TNF）和白细胞介素2（IL2）的产生。仅用TDF治疗的癌症显示免疫应答没有显着变化。

“通过对所有治疗时间点和参考急性乙型肝炎对照组的所有数据进行分级聚类分析，可以很好地说明用GS-4774和替诺福韦联合治疗的患者T细胞反应的演变。免疫反应能够自发地控制感染，“科学家写道。

GS-4774通常耐受良好。与注射部位相关的最常见的治疗引起的不良事件包括疼痛，红斑和肿胀，而其他常见事件包括疲劳和头痛。

“”包括疫苗在内的未来联合疗法应考虑通过降低抗原负荷来改善T细胞对抗原刺激的反应性的药物的顺序给药，例如沉默RNA化合物或衣壳装配抑制剂，或通过抑制免疫检查点或调整T细胞代谢，然后通过疫苗接种进行T细胞和B细胞增强，“Boni及其同事总结道。 - 作者：Talitha Bennett

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