Department of Virology, Pasteur Institute of Iran, Tehran, Iran.
Department of Parasitology, Pasteur Institute of Iran, Tehran, Iran.
J Immunol Res. 2018 May 3;2018:9464186. doi: 10.1155/2018/9464186. eCollection 2018.
-derived concatenated, multitype L2-conserved epitopes of human papillomavirus (HPV) L2 protein might represent a less expensive and pan-type vaccine alternative (compared to type-specific HPV L1 virus-like particles), if stable protein expression and strong immunogenicity features could be met. Herein, three dual-type- (DT-) HPV L2 fusion peptides comprising the three head-to-tail tandem repeats (multimers) of either HPV 16 epitope "17-36" or "69-81" or one copy (monomer) of 11-88 fused to the same residues of HPV 18 were constructed and expressed in . SDS-PAGE and Western blot analyses indicated the proper expression and stability of the -derived DT peptides. Mice immunized by formulation of the purified DT peptides and Freund's adjuvant (CFA/IFA) raised neutralizing antibodies (NAbs; the highest for DT: 11-88 peptide) which showed proper cross-reactivity to HPV types: 18, 16, 31, and 45 and efficiently neutralized HPV 18/16 pseudoviruses . Immunization studies in mice by formulation of the DT: 11-88 × 1 peptide with various adjuvants (alum, MF59, and Montanides ISA 720 and 50) indicated that Montanide adjuvants elicited the highest cross-reactive titers of NAbs and similar levels of IgG1 and IgG2a (switching towards balanced Th1/Th2 responses). The results implied development of low-cost -derived DT: 11-88 peptide formulated in human compatible ISA 720 adjuvant as a HPV vaccine.
由人乳头瘤病毒（HPV）L2 蛋白衍生的串联、多型 L2 保守表位可能代表一种更廉价的泛型疫苗替代物（与特定型 HPV L1 病毒样颗粒相比），如果能够满足稳定的蛋白表达和强免疫原性特征。在此，构建并表达了三种双型（DT）HPV L2 融合肽，它们包含 HPV 16 表位“17-36”或“69-81”的三个头尾串联重复（多聚体）或一个拷贝（单体）11-88 融合到 HPV 18 的相同残基上。SDS-PAGE 和 Western blot 分析表明，-衍生的 DT 肽得到了正确表达和稳定。用纯化的 DT 肽和弗氏佐剂（CFA/IFA）制剂免疫小鼠，产生了中和抗体（NAb；最高的是 DT：11-88 肽），该抗体对 HPV 型别显示出适当的交叉反应性：18、16、31 和 45，并有效地中和了 HPV 18/16 假病毒。用不同佐剂（铝佐剂、MF59 和 Montanide ISA 720 和 50）制剂对 DT：11-88 ⁇ × ⁇ 1 肽进行的小鼠免疫研究表明，Montanide 佐剂引起了最高的 NAb 交叉反应性滴度和相似水平的 IgG1 和 IgG2a（向平衡 Th1/Th2 反应转换）。这些结果暗示了在人类相容的 ISA 720 佐剂中开发低成本的 -衍生 DT：11-88 肽作为 HPV 疫苗。
