Precisely Shaped Self-Adjuvanting Peptide Vaccines with Enhanced Immune Responses for HPV-Associated Cancer Therapy,ACS Applied Materials & Interfaces

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Precisely Shaped Self-Adjuvanting Peptide Vaccines with Enhanced Immune Responses for HPV-Associated Cancer Therapy
ACS Applied Materials & Interfaces ( IF 8.3 ) Pub Date : 2021-10-14 , DOI: 10.1021/acsami.1c15361
Yanqiu Song ₁ , Qi Su ₂ , Huijuan Song ₂ , Xiaoguang Shi ₁ , Mingming Li ₁ , Na Song ₁ , Shaofeng Lou ₁ , Weiwei Wang ₂ , Zhilin Yu ₁

Affiliation

Peptide vaccines exhibit great potential in cancer therapy via eliciting antigen-specific host immune response and long-term immune memory to defend cancer cells. However, the low induced immune response of many developing vaccines implies the imperatives for understanding the favorable structural features of efficient cancer vaccines. Herein, we report on the two groups of self-adjuvanting peptide vaccines with distinct morphology and investigate the relationship between the morphology of peptide vaccines and the induced immune response. Two nanofibril peptide vaccines were created via co-assembly of a pentapeptide with a central 4-aminoproline residue, with its derivative functionalized with antigen epitopes derived from human papillomavirus E7 proteins, whereas utilization of a pentapeptide with a natural proline residue led to the formation of two nanoparticle peptide vaccines. The immunological results of dendritic cell (DCs) maturation and antigen presentation induced by the peptide assemblies implied the self-adjuvanting property of the resulting peptide vaccines. In particular, cellular uptake studies revealed the enhanced internalization and elongated retention of the nanofibril peptide vaccines in DCs, leading to their advanced performance in DC maturation, accumulation at lymph nodes, infiltration of cytotoxic T lymphocytes into tumor tissues, and eventually lysis of in vivo tumor cells, compared to the nanoparticle counterparts. The antitumor immune response caused by the nanofibril peptide vaccines was further augmented when simultaneously administrated with anti-PD-1 checkpoint blockades, suggesting the opportunity of the combinatorial immunotherapy by utilizing the nanofibril peptide vaccines. Our findings strongly demonstrate a robust relationship between the immune response of peptide vaccines and their morphology, thereby elucidating the critical role of morphological control in the design of efficient peptide vaccines and providing the guidance for the design of efficient peptide vaccines in the future.

中文翻译：

用于 HPV 相关癌症治疗的具有增强免疫反应的精确成型自我调节肽疫苗

肽疫苗通过引发抗原特异性宿主免疫反应和长期免疫记忆来保护癌细胞，在癌症治疗中表现出巨大的潜力。然而，许多正在开发的疫苗的低诱导免疫反应意味着必须了解有效癌症疫苗的有利结构特征。在此，我们报告了两组具有不同形态的自佐剂肽疫苗，并研究了肽疫苗的形态与诱导的免疫反应之间的关系。通过五肽与中心 4-氨基脯氨酸残基的共组装产生了两种纳米纤维肽疫苗，其衍生物被人乳头瘤病毒 E7 蛋白衍生的抗原表位功能化，而使用具有天然脯氨酸残基的五肽导致两种纳米颗粒肽疫苗的形成。肽组装体诱导的树突状细胞 (DC) 成熟和抗原呈递的免疫学结果暗示了所得肽疫苗的自佐剂特性。特别是，细胞摄取研究揭示了纳米纤维肽疫苗在 DC 中的增强内化和延长保留，导致它们在 DC 成熟、淋巴结积累、细胞毒性 T 淋巴细胞浸润到肿瘤组织中以及最终在体内溶解方面具有先进的性能肿瘤细胞，与纳米颗粒对应物相比。当与抗 PD-1 检查点阻断剂同时给药时，由纳米纤维肽疫苗引起的抗肿瘤免疫反应进一步增强，这表明利用纳米纤维肽疫苗进行组合免疫治疗的机会。我们的研究结果有力地证明了多肽疫苗的免疫反应与其形态之间存在密切的关系，从而阐明了形态控制在高效多肽疫苗设计中的关键作用，并为未来高效多肽疫苗的设计提供了指导。

更新日期：2021-10-27

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