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用于鉴定人乳头瘤病毒18型免疫治疗表位的全面计算机模拟分析

A Comprehensive in Silico Analysis for Identification of Immunotherapeutic Epitopes of HPV-18.

作者信息

Gupta Bharti, Kumar Anoop, Sridevi Parikipandla

机构信息

Department of Biotechnology, Faculty of Science, Indira Gandhi National Tribal University, Amarkantak, 484887 Madhya Pradesh India.

National Institute of Biologicals, Noida, India.

出版信息

Int J Pept Res Ther. 2021;27(4):2717-2726. doi: 10.1007/s10989-021-10285-x. Epub 2021 Sep 20.

Abstract

Human papillomavirus (HPV) remains the major cause of cervical cancer, globally. High risk HPV (Hr-HPV) 16 and 18 together account for more than 70% of cervical cancer cases, whereas the hr-HPV-18 is the second most prevalent hr-HPV type, causing about 5.2% of all cancers worldwide. Considering the high prevalence and mortality rate, cervical cancer remains a noteworthy health problem among women. As of now, no registered immunotherapies are available after the HPV infection. Thus, developing an immunotherapeutic candidate against hr-HPV would be of major clinical benefit. Nowadays, the T-and B-cell peptide based targeted vaccines have been considered as the best candidate for vaccine development against viral infections. In this study, both prophylactic and therapeutic vaccine candidates against hr-HPV-18 were predicted. To achieve this, the prediction of T-and B-cell epitopes of major histocompatibility complex (MHC) were accomplished, that can be used for HPV immunotherapy. For MHC-I, a maximum number (20) of potent peptides were found, against HLA-B51:01 (L1 = 9, L2 = 6, E2 = 4, and E4 = 1) having percentile value < 1 and, immunogenicity scores higher than 0.5, followed by HLA-A11:01 (L1 = 8, E2 = 7 L2 = 2, and E6 = 1, E7 = 1); 19 epitopes. For MHC-II, the highest number of peptides found, against the HLA-DRB104:01 (L2 = 10, E5 = 7, and E4 = 4), HLA-DRB104:05 (E5 = 7, E2 = 5, E4 = 5, and L1 = 4) HLA-DPA101:03/DPB104:01 (E7 = 7, E6 = 5, L2 = 5, and E2 = 2), HLA-DRB5*01:01(E6 = 6, L1 = 6, and L2 = 6); peptides 21, 21, 19 and 18 respectively. For B-cell, total 94, 16 amino acid long B-cell epitopes were predicted. In conclusion, these predicted epitopes can be valuable candidates for in vitro or in vivo therapeutic vaccine studies against hr-HPV-18 associated cancer.

摘要

人乳头瘤病毒(HPV)仍是全球宫颈癌的主要病因。高危型HPV(Hr-HPV)16型和18型共同导致了超过70%的宫颈癌病例,而Hr-HPV-18型是第二常见的高危型HPV类型,导致全球约5.2%的所有癌症。鉴于其高发病率和死亡率,宫颈癌仍是女性中一个值得关注的健康问题。截至目前,HPV感染后尚无注册的免疫疗法。因此,开发一种针对高危型HPV的免疫治疗候选药物将具有重大临床益处。如今,基于T细胞和B细胞肽的靶向疫苗被认为是针对病毒感染进行疫苗开发的最佳候选药物。在本研究中,预测了针对Hr-HPV-18的预防性和治疗性疫苗候选物。为实现这一目标,完成了主要组织相容性复合体(MHC)的T细胞和B细胞表位预测,这些表位可用于HPV免疫治疗。对于MHC-I,发现了最多数量(20个)的有效肽,针对百分位数<1且免疫原性评分高于0.5的HLA-B51:01(L1 = 9,L2 = 6,E2 = 4,E4 = 1),其次是HLA-A11:01(L1 = 8,E2 = 7,L2 = 2,E6 = 1,E7 = 1);19个表位。对于MHC-II,发现针对HLA-DRB104:01(L2 = 10,E5 = 7,E4 = 4)、HLA-DRB104:05(E5 = 7,E2 = 5,E4 = 5,L1 = 4)、HLA-DPA101:03/DPB104:01(E7 = 7,E6 = 5,L2 = 5,E2 = 2)、HLA-DRB5*01:01(E6 = 6,L1 = 6,L2 = 6)的肽数量最多;分别为21个、21个、19个和18个肽。对于B细胞,共预测了94个16个氨基酸长的B细胞表位。总之,这些预测的表位可能是针对与Hr-HPV-18相关癌症的体外或体内治疗性疫苗研究的有价值候选物。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/a16c/8451162/915960139985/10989_2021_10285_Fig1_HTML.jpg

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