| 马铭饶,郝亚茹,张 婷,刘洪洋,王志荣,夏百成,周 艳,许雪梅.HPV18 L2保守中和表位肽协同MF59与CpG-ODN免疫可诱发广谱中和抗体反应[J].,2020,(20):3801-3806 |
| HPV18 L2保守中和表位肽协同MF59与CpG-ODN免疫可诱发广谱中和抗体反应 |
| Conservative Neutralizing Epitope of Human Papillomavirus Type 18 L2 Immunized with MF59 and CpG-ODN Can Induce Broad-spectrum Neutralizing Antibodies |
| 投稿时间：2020-06-23 修订日期：2020-07-18 |
| DOI：10.13241/j.cnki.pmb.2020.20.001 |
| 中文关键词: 人乳头瘤病毒18型 L2保守中和表位 广谱中和抗体 |
| 英文关键词: Human papillomavirus type 18 L2 conservative neutralizing epitope Broad-spectrum neutralizing antibody |
| 基金项目:中国医学科学院医学与健康科技创新工程项目基金(2016-I2M-3-026)；中国医学科学院医学与健康科技创新工程项目基金(2020-I2M-2-014)；国家自然科学基金面上项目(31970867) |
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| 中文摘要: |
| 摘要 目的：人乳头瘤病毒(HPV)次要外壳蛋白L2保守中和表位肽可诱发交叉中和抗体，研究L2保守中和表位肽免疫原性的特点利于HPV通用疫苗的研发。HPV18是第二常见的优势流行高危型，但18L2保守表位肽的免疫活性未见报道。方法：本研究采用化学法合成HPV18 L2N端多肽(18RG-1)并偶联KLH获得18RG1-KLH肽；联合MF59/CpG-ODN复合佐剂或弗氏佐剂皮下免疫BALB/c小鼠5次，用假病毒中和实验检测抗血清针对α6、α7、α9及α11亚属中多个致癌型HPV的中和抗体。结果： MF59/CpG-ODN复合佐剂多肽组抗血清对所有6种检测型别的中和活性与弗氏佐剂多肽组的相当。MF59/CpG-ODN佐剂多肽组抗血清具有广谱中和活性，中和范围至少包括14种致癌型HPV，中和抗体滴度最高的为HPV45 (438)和HPV18 (325)，其次为HPV68 (163)和HPV70 (150)，这四种优势中和型别均为α7亚属。结论：首次发现HPV18 L2 RG1保守中和表位免疫血清可诱发广谱中和抗体反应 (其中对α7亚属的HPV中和活性最强，为优势中和型别)。研究结果为基于L2保守表位的广谱HPV疫苗研发奠定基础。 |
| 英文摘要: |
| ABSTRACT Objective: The human papillomavirus (HPV) minor coat protein L2 contains conservative neutralizing epitope which can induce cross-neutralizing antibodies. It is beneficial to analyze the immunogenicity of L2 conservative neutralizing epitopes for the development of HPV universal vaccines. HPV18 is the second most prevalent high-risk type worldwide, but the immunogenicity of the 18L2 peptide has not been reported. Methods: HPV18 L2 peptide (18RG-1) was synthesized by chemical methods and conjugated with KLH to construct 18RG1-KLH; BALB/c mice were immunized five times with MF59/CpG-ODN or Freud's Adjuvant. Neutralizing antibodies against oncogenic HPVs from α6, α7, α9 and α11 species were detected by pseudovirus neutralization assay. Results: The neutralizing activity of the antiserum of the MF59/CpG-ODN group against all 6 detected types is equivalent to that of the Freund's Adjuvant group. The antiserum of the MF59/CpG-ODN group ,which can at least neutralize 14 oncogenic HPVs, has broad-spectrum neutralizing activity. The highest neutralizing antibody titers are against HPV45 (438) and HPV18 (325), followed by HPV68 (163) and HPV70 (150), all belong to α7 specie. Conclusion: It is discovered for the first time that conservative neutralizing epitope HPV18 L2RG1 can induce broad-spectrum neutralizing activity (neutralizing activity against α7 species is the strongest). The results lay the foundation of the development of broad-spectrum HPV vaccines based on L2 conserved epitopes. |
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