Department of Microbial Biotechnology, Genetic Engineering Division, National Research Centre, 33 EL Bohouth Street, Dokki, Giza 12622, Egypt.
Biological Anthropology Department, Medical Research Division, National Research Centre, Dokki, Giza, Egypt.
J Infect Public Health. 2021 Feb;14(2):169-178. doi: 10.1016/j.jiph.2020.12.006. Epub 2020 Dec 15.
The striking difference in severity of SARS CoV2 infection among global population is partly attributed to viral factors. With the spike (S) and nucleocapsid (N) are the most immunogenic subunits, genetic diversity and antigenicity of S and N are key players in virulence and in vaccine development.
This paper aims at identifying immunogenic targets for better vaccine development and/or immunotherapy of COVID 19 pandemic.
18 complete genomes of SARS CoV2 (n=14), SARS CoV (n=2) and MERS CoV (n=2) were examined. Bioinformatics of viral genetics and protein folding allowed functional tuning of NH2 Terminal Domain (NTD) of S protein and development of epitope maps for B and T cell responses.
A deletion of amino acid residues Y144 and G107 were discovered in NTD of S protein derived from Indian and French isolates resulting in altered pocket structure exclusively located in NTD and reduced affinity of NTD binding to endogenous nAbs and disrupted NTD mediated cell entry. We therefore, proposed a set of B and T cell epitopes based on Immune Epitope Database, homologous epitopes for nAbs in convalescent plasma post SARS CoV infection and functional domains of S (NTD, Receptor Binding domain and the unique polybasic Furin cleavage site at S1/S2 junction). Nevertheless, laboratory data are required to develop vaccine and immunotherapeutics.
全球人群中严重程度不同的 SARS-CoV-2 感染部分归因于病毒因素。刺突（S）和核衣壳（N）是最具免疫原性的亚单位，S 和 N 的遗传多样性和抗原性是病毒毒力和疫苗开发的关键因素。
本文旨在确定免疫原性靶标，以更好地开发 COVID-19 大流行的疫苗和/或免疫疗法。
检查了 18 株完整的 SARS-CoV-2（n=14）、SARS-CoV（n=2）和 MERS-CoV（n=2）基因组。病毒遗传学和蛋白质折叠的生物信息学允许对 S 蛋白的 NH2 末端结构域（NTD）进行功能调整，并开发 B 细胞和 T 细胞反应的表位图谱。
在源自印度和法国分离株的 S 蛋白的 NTD 中发现了氨基酸残基 Y144 和 G107 的缺失，导致口袋结构发生改变，仅位于 NTD 中，降低了 NTD 与内源性 nAbs 的结合亲和力，并破坏了 NTD 介导的细胞进入。因此，我们根据免疫表位数据库、SARS-CoV 感染后恢复期血浆中的 nAbs 同源表位以及 S 的功能域（NTD、受体结合域和 S1/S2 交界处独特的多碱性弗林切割位点）提出了一组 B 和 T 细胞表位。然而，需要实验室数据来开发疫苗和免疫疗法。
