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寨卡病毒潜在抗原性CTL表位的计算预测与分析:迈向疫苗研发的第一步。

Computational prediction and analysis of potential antigenic CTL epitopes in Zika virus: A first step towards vaccine development.

作者信息

Dikhit Manas R, Ansari Md Yousuf, Mansuri Rani, Sahoo Bikash R, Dehury Budheswar, Amit Ajay, Topno Roshan K, Sahoo Ganesh C, Ali Vahab, Bimal Sanjiva, Das Pradeep

机构信息

Department of Bioinformatics, Rajendra Memorial Research Institute of Medical Sciences, Patna 800007, India.

Department of Bioinformatics, Rajendra Memorial Research Institute of Medical Sciences, Patna 800007, India; Department of Pharmacoinformatics and Biotechnology, National Institute of Pharmaceutical Education and Research, Hajipur 844102, India.

出版信息

Infect Genet Evol. 2016 Nov;45:187-197. doi: 10.1016/j.meegid.2016.08.037. Epub 2016 Aug 31.

Abstract

The Zika virus disease is an Aedes mosquito-borne disease caused by the ZIKA virus. The unavailability of vaccines or proper chemotherapeutic treatment emphasizes the need for the development of preventive and therapeutic vaccines. T cell specific epitopes have been used as vaccine candidates to generate desired immune responses against a variety of viral pathogens. Herein, the immune-informatics approach was used for the screening of potential major histocompatibility complex class I restricted epitopes, which may be competent to generate a cell-mediated immune response in humans. A total of 63 epitopes were identified, which revealed a comprehensive binding affinity to the 42 different human leukocyte antigen class I supertypes: A01, A02, A08, A23, A24, A25, A26, A29, A30, A32, A66, A68, A69, A80, B07, B08, B14, B15, B27, B35, B39, B40, B42, B45, B46, B48, B51, B53, B54, B57, B58, B83, C12, C03, C04, C05, C06, C07, C08, C12, C14, and C15, and which had no homologs in humans. By combining the human leukocyte antigen binding specificity and population coverage, nine promiscuous epitopes located in Capsid 1 Protein (MVLAILAFL(P1)), Envelop Protein (RLKGVSYSL (P2) and RLITANPVI (P3)), NS2A (AILAALTPL (P4)), NS4B (LLVAHYMYL (P5) and LVAHYMYLI (P6)) and NS5 (SLINGVVRL (P7), ALNTFTNLV (P8) and YLSTQVRYL (P9)) were shortlisted. Most of these consensus epitopes revealed 100% conservancy in all Zika virus strains and were very less conserved against the human proteome. The combination of the selected epitopes accounted for an optimal coverage in the world wide population (>99%) independent of ethnicity. Structural analysis of these selected epitopes by the PatchDock web server showed their preferential mode of presentation to the T cell receptor. All these results recommended the possibility of a combined epitope vaccine strategy and can therefore be further investigated for their immunological relevance and usefulness as vaccine candidates.

摘要

寨卡病毒病是一种由寨卡病毒引起的经伊蚊传播的疾病。由于缺乏疫苗或适当的化疗治疗方法,因此迫切需要开发预防性和治疗性疫苗。T细胞特异性表位已被用作疫苗候选物,以产生针对多种病毒病原体的所需免疫反应。在此,采用免疫信息学方法筛选潜在的主要组织相容性复合体I类限制性表位,这些表位可能能够在人体内产生细胞介导的免疫反应。共鉴定出63个表位,这些表位对42种不同的人类白细胞抗原I类亚型(A01、A02、A08、A23、A24、A25、A26、A29、A30、A32、A66、A68、A69、A80、B07、B08、B14、B15、B27、B35、B39、B40、B42、B45、B46、B48、B51、B53、B54、B57、B58、B83、C12、C03、C04、C05、C06、C07、C08、C12、C14和C15)具有全面的结合亲和力,且在人类中无同源物。通过结合人类白细胞抗原结合特异性和人群覆盖率,筛选出位于衣壳1蛋白(MVLAILAFL(P1))、包膜蛋白(RLKGVSYSL (P2)和RLITANPVI (P3))、NS2A(AILAALTPL (P4))、NS4B(LLVAHYMYL (P5)和LVAHYMYLI (P6))以及NS5(SLINGVVRL (P7)、ALNTFTNLV (P8)和YLSTQVRYL (P9))中的9个多聚表位。这些共有表位中的大多数在所有寨卡病毒株中显示出100%的保守性,而与人类蛋白质组的保守性极低。所选表位的组合在全球人群中(>99%)实现了最佳覆盖率,且与种族无关。通过PatchDock网络服务器对这些所选表位进行结构分析,显示了它们呈递给T细胞受体的优先模式。所有这些结果表明联合表位疫苗策略具有可行性,因此可进一步研究其免疫相关性以及作为疫苗候选物的实用性。

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