HBV衍生的合成长肽可以提高慢性HBV患者体内的CD4 +和CD8 + T细

StephenW

HBV-Derived Synthetic Long Peptide Can Boost CD4+ and CD8+ T-Cell Responses in Chronic HBV Patients Ex Vivo
Yingying Dou Nadine van Montfoort Aniek van den Bosch Robert A de Man Gijs G Zom Willem-Jan Krebber Cornelis J M Melief Sonja I Buschow Andrea M Woltman
The Journal of Infectious Diseases, Volume 217, Issue 5, 14 February 2018, Pages 827–839, https://doi.org/10.1093/infdis/jix614
Published:
06 December 2017

Abstract
Background

Vaccination with synthetic long peptides (SLP) is a promising new treatment strategy for chronic hepatitis B virus (CHB). SLP can induce broad T-cell responses for all HLA types. Here we investigated the ability of a prototype HBV-core (HBc)-sequence-derived SLP to boost HBV-specific T cells in CHB patients ex vivo.
Methods

HBc-SLP was used to assess cross-presentation by monocyte-derived dendritic cells (moDC) and BDCA1+ blood myeloid DC (mDC) to engineered HBV-specific CD8+ T cells. Autologous SLP-loaded and toll-like receptor (TLR)-stimulated DC were used to activate patient HBc-specific CD8+ and CD4+ T cells.
Results

HBV-SLP was cross-presented by moDC, which was further enhanced by adjuvants. Patient-derived SLP-loaded moDC significantly increased autologous HBcAg18-27-specific CD8+ T cells and CD4+ T cells ex vivo. HBV-specific T cells were functional as they synthesized tumor necrosis factor-alpha and interferon-gamma. In 6/7 of patients blockade of PD-L1 further increased SLP effects. Also, importantly, patient-derived BDCA1+ mDC cross-presented and activated autologous T-cell responses ex vivo.
Conclusions

As a proof of concept, we showed a prototype HBc-SLP can boost T-cell responses in patients ex vivo. These results pave the way for the development of a therapeutic SLP-based vaccine to induce effective HBV-specific adaptive immune responses in CHB patients.

StephenW

HBV衍生的合成长肽可以提高慢性HBV患者体内的CD4 +和CD8 + T细胞应答体外
Yingying Dou Nadine van Montfoort Aniek van den Bosch Robert A de Man Gijs G Zom Willem-Jan Krebber Cornelis J M Melief Sonja I Buschow Andrea M Woltman
The Journal of Infectious Diseases，Volume 217，Issue 5，February 2018，Pages 827-839，https://doi.org/10.1093/infdis/jix614
发布时间：
2017年12月6日

抽象
背景

用合成的长肽（SLP）进行疫苗接种是治疗慢性乙型肝炎病毒（CHB）的有希望的新治疗策略。 SLP可以诱导所有HLA类型的广泛的T细胞应答。在这里，我们调查了原型HBV核心（HBc）序列衍生SLP在CHB患者体外提高HBV特异性T细胞的能力。
方法

使用HBc-SLP来评估单核细胞衍生的树突细胞（moDC）和BDCA1 +血液髓样DC（mDC）对工程改造的HBV特异性CD8 + T细胞的交叉呈递。使用自体SLP负载的和Toll样受体（TLR）刺激的DC来激活患者HBc特异性CD8 +和CD4 + T细胞。
结果

通过moDC交叉呈递HBV-SLP，其通过佐剂进一步增强。来自患者的SLP装载的moDC显着增加离体自体HBcAg18-27特异性CD8 + T细胞和CD4 + T细胞。 HBV特异性T细胞在合成肿瘤坏死因子-α和干扰素-γ时起作用。在6/7的患者中，PD-L1的阻断进一步增加了SLP的作用。此外，重要的是，患者来源的BDCA1 + mDC在体外交叉呈递和激活自体T细胞应答。
结论

作为概念证明，我们展示了一个原型HBc-SLP可以促进患者体外T细胞反应。这些结果为开发治疗性SLP疫苗以在CHB患者中诱导有效的HBV特异性适应性免疫应答铺平了道路。

StephenW

https://academic.oup.com/jid/article/217/5/827/4705967