中文摘要：本研究利用细菌表达系统构建了重组HPV16 E7和NT-gp96蛋白。分别以Montanide、HP91和NT-gp96作为佐剂，采用E7抗原免疫小鼠，并分析他们的保护作用和治疗效果。结果表明：采用HP91肽作为佐剂的E7抗原能够诱导产生更高水平的IgG2a和IFN-γ，与其他试验组相比，能够诱导产生Th1细胞内免疫。该结果表明，Hp91肽是一种抗rNT-gp96病原感染的安全有效的佐剂，能够具有与Montanide佐剂类似的抗肿瘤作用。
 
外文摘要：Up to now, different protein vaccine modalities against human papillomavirus (HPV) have been designed to control cervical cancer. The important issue is to increase their immunogenicity using appropriate adjuvants. Among heat shock proteins (HSPs), glycoprotein 96 (Gp96) and its N-terminal region (NT-gp96) have attracted a specific interest in stimulation of antigen-specific immune responses in vivo. Furthermore, the potency of high mobility group box 1 (HMGB1) protein and its fragment (Hp91) was reported to enhance the desired immune responses against various disorders. In this study, the recombinant (r) HPV16 E7 and rNT-gp96 proteins were generated in bacterial expression system. Mice were vaccinated three times with E7 antigen mixed with Montanide, Hp91, and NT-gp96 as the adjuvant and their preventive and therapeutic efficiencies were evaluated in a murine tumor model. Mice vaccinated with E7 co-delivered by Hp91 peptide induced higher IgG2a and IFN-gamma. responses in comparison with E7 co-injected with Montanide and NT-gp96 protein suggesting a strong Th1 cellular immune response. The data showed that vaccination with non-covalent rE7 + rNT-gp96 complex delayed the tumor growth as compared to control groups. Mice immunized with rE7 + Montanide and rE7 + Hp91 protected 100% of mice versus 75% survival in groups vaccinated with rE7 + rNT-gp96 after TC-1 tumor challenge. The percentage of tumor free mice was decreased in group immunized with rE7 + rNT-gp96 in therapeutic experiments (similar to 50%). These results demonstrated that Hp91 peptide is a safe and strong adjuvant against rNT-gp96 with the potent anti-tumor effects similar to Montanide adjuvant.
外文关键词：Human papillomavirus; heat shock protein; Gp96; HMGB1; protein vaccine; E7
作者：Talebi, S; Bolhassani, A; Azad, TM; Arashkia, A; Modaresi, MH
作者单位：伊朗巴斯德研究所
期刊名称：PROTEIN AND PEPTIDE LETTERS
期刊影响因子：0.964
出版年份：2017
出版刊次：3
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