Intranasal immunization with synthetic peptides corresponding to the E6 and E7 oncoproteins of human papillomavirus type 16 induces systemic and mucosal cellular immune responses and tumor protection.
Intranasal immunization with synthetic peptides corresponding to the E6 and E7 oncoproteins of human papillomavirus type 16 induces systemic and mucosal cellular immune responses and tumor protection.
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DOI：
10.1016/j.vaccine.2007.01.010
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发表时间：
2007-04
期刊：
影响因子：
5.5
通讯作者：
P. Manuri;B. Nehete;P. Nehete;R. Reisenauer;S. Wardell;Amy N. Courtney;Ratish Gambhira;Dakshyani Lomada;A. Chopra;K. Sastry
中科院分区：
文献类型：
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作者：
P. Manuri;B. Nehete;P. Nehete;R. Reisenauer;S. Wardell;Amy N. Courtney;Ratish Gambhira;Dakshyani Lomada;A. Chopra;K. Sastry
高危HPV 16型的E6和E7癌蛋白代表了HPV疫苗开发的理想靶点，它们在宫颈癌病变中持续表达。由于HPV-16主要通过生殖器粘膜途径传播，因此粘膜免疫应答构成了针对HPV相关病变的疫苗接种策略的基本特征。我们在此提供的证据表明，使用突变型霍乱毒素佐剂（CT-2*），通过鼻内途径用分别来自HPV-16的E7和E6癌蛋白的肽E744- 62和E643- 57的混合物粘膜免疫小鼠，在全身和粘膜组织中引发强烈的抗原特异性细胞免疫应答。观察到CD 4和CD 8细胞产生显著水平的IFN-γ，同时沿着CTL应答，其有效对抗肽脉冲靶以及表达同源E6和E7蛋白的同源肿瘤细胞（TC-1）。此外，用肽混合物和CT-2* 免疫的小鼠有效地抵抗TC-1肿瘤攻击。这些结果与我们早期观察到的T细胞对这些肽的应答与HPV相关的宫颈上皮内瘤变的消融治疗后妇女的无复发生存相关，支持这些E6和E7肽用于包含在疫苗制剂中的潜力。
The E6 and E7 oncoproteins of the high-risk HPV type16 represent ideal targets for HPV vaccine development, they being consistently expressed in cervical cancer lesions. Since HPV-16 is primarily transmitted through genital mucosal route, mucosal immune responses constitute an essential feature for vaccination strategies against HPV-associated lesions. We present here evidence showing that mucosal immunization of mice by the intranasal route with a mixture of peptides E744–62and E643–57from the E7 and E6 oncoproteins of HPV-16, respectively, using a mutant cholera toxin adjuvant (CT-2*), primed strong antigen-specific cellular immune responses in systemic and mucosal tissues. Significant levels of IFN-γ production by both CD4 and CD8 cells were observed along with CTL responses that were effective against both peptide-pulsed targets as well as syngeneic tumor cells (TC-1) expressing the cognate E6 and E7 proteins. Furthermore, mice immunized with the peptide mixture and CT-2*effectively resisted TC-1 tumor challenge. These results together with our earlier observations that T cell responses to these peptides correlate with recurrence-free survival in women after ablative treatment for HPV-associated cervical intraepithelial neoplasia, support the potential of these E6 and E7 peptides for inclusion in vaccine formulations.