<br>Hp91 免疫佐剂：一种 HMGB1 衍生肽，用于开发治疗性 HPV 疫苗,Biomedicine & Pharmacotherapy

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Hp91 免疫佐剂：一种 HMGB1 衍生肽，用于开发治疗性 HPV 疫苗
Biomedicine & Pharmacotherapy ( IF 6.9 ) Pub Date : 2016-12-05 , DOI: 10.1016/j.biopha.2016.11.115
Somayeh Talebi ₁ , Azam Bolhassani ₁ , Seyed Mehdi Sadat ₁ , Rouhollah Vahabpour ₂ , Elnaz Agi ₁ , Sepideh Shahbazi ₁

Affiliation

高比例的人类宫颈恶性肿瘤与人乳头瘤病毒（HPV）感染有关。因此，在各种治疗性HPV疫苗中寻找新的非侵入性治疗策略非常重要。在当前的研究中，我们使用 HPV16 E7 作为模型抗原，研究了基于 DNA 和蛋白质的疫苗在肿瘤小鼠模型中的保护和治疗效果。在该系列中，全长高迁移率族盒 1 (HMGB1) 蛋白以及 HMGB1 衍生的短肽 (Hp91) 被用作刺激适应性免疫和开发这些疫苗效力的佐剂。以复合和缀合形式用 HMGB1 进行 HPV16 E7 的 DNA 疫苗接种。将 Hp91 肽以及 Hp121 对照肽的免疫刺激特性与 Montanide 720 在蛋白质疫苗接种中进行比较。我们的数据显示，HPV16 E7 蛋白与 Hp91 肽或 Hp91+Hp121 肽的联合免疫显着增加了 IFN-γ 的分泌、IgG2a 抗体反应，并保护 100% 的小鼠免受 TC-1 肿瘤攻击。此外，HMGB1与E7抗原的连接导致DNA疫苗的免疫原性增强，尤其是与Hp91和Hp121肽组合时。这些发现表明，Hp91 肽和全长 HMGB1 基因可能分别成为改进治疗性 HPV 蛋白疫苗和 DNA 疫苗的有效佐剂。

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Hp91 immunoadjuvant: An HMGB1-derived peptide for development of therapeutic HPV vaccines

High percentage of human cervical malignancy is related to human papillomavirus (HPV) infections. Thus, it is important to find novel non-invasive treatment strategies among various therapeutic HPV vaccines. In current study, we investigated the protective and therapeutic effects of DNA- and protein-based vaccines using HPV16 E7 as a model antigen in tumor mice model. In this line, the full length of high-mobility group box 1 (HMGB1) protein as well as an HMGB1-derived short peptide (Hp91) was used as an adjuvant for stimulating adaptive immunity and developing the potency of these vaccines. DNA vaccination of HPV16 E7 with HMGB1 was performed as the complexed and conjugated forms. The immunostimulatory properties of Hp91 peptide along with Hp121 control peptide were compared to Montanide 720 in protein vaccination. Our data showed that co-immunization of HPV16 E7 protein with Hp91 peptide or Hp91+Hp121 peptides significantly increased the secretion of IFN-γ, IgG2a antibody response, and protected 100% of mice against a TC-1 tumor challenge. Furthermore, the linkage of HMGB1 with E7 antigen led to enhance the immunogenicity of DNA vaccine especially in combination with Hp91 and Hp121 peptides. These findings suggest that Hp91 peptide, and the full length of HMGB1 gene could be an efficient adjuvant for improvement of therapeutic HPV protein- and DNA-based vaccines, respectively.

更新日期：2016-12-05

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