Large-Scale Structure-Based Screening of Potential T Cell Cross-Reactivities Involving Peptide-Targets From BCG Vaccine and SARS-CoV-2.
Large-Scale Structure-Based Screening of Potential T Cell Cross-Reactivities Involving Peptide-Targets From BCG Vaccine and SARS-CoV-2.
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DOI：
10.3389/fimmu.2021.812176
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发表时间：
2021
影响因子：
7.3
通讯作者：
de Souza APD
中科院分区：
文献类型：
--
作者：
Tarabini RF;Rigo MM;Faustino Fonseca A;Rubin F;Bellé R;Kavraki LE;Ferreto TC;Amaral Antunes D;de Souza APD
虽然这不是第一次影响人类的病毒大流行，但我们现在第一次面临由冠状病毒引起的大流行。严重急性呼吸系统综合征冠状病毒2 （SARS-CoV-2）是导致全球450多万人死亡的COVID-19大流行的罪魁祸首。尽管付出了前所未有的努力，随着疫苗在创纪录的时间内开发出来，SARS-CoV-2继续在世界范围内传播，不同国家出现了新的变体。这种持续传播在一定程度上是由于在一些国家公众对疫苗接种的抵制，以及在其他国家获得疫苗的机会有限。有限的疫苗接种覆盖率、耐药变异的持续风险以及冠状病毒天然储存库的存在，突出了制定针对SARS-CoV-2和其他冠状病毒的额外治疗策略的重要性。在大流行开始时，有人提出，实施卡介苗疫苗接种计划的国家可能与COVID-19病例数量和/或严重程度降低有关。初步研究为这种关系提供了证据，正在进行的临床试验中进行进一步调查。卡介苗接种诱导的对SARS-CoV-2的保护可能是由交叉反应性T细胞淋巴细胞介导的，其识别受感染细胞表面I类人白细胞抗原（hla - 1）所显示的肽。为了确定T细胞交叉反应的潜在靶点，我们实施了基于序列和基于结构的方法相结合的计算机策略，从BCG和SARS-CoV-2中筛选了超过1350万个可能的交叉反应肽对。我们的研究产生了(i)免疫原性bcg衍生肽的列表，这些肽可能引发T细胞对SARS-CoV-2的交叉反应，（ii）为筛选的靶点建模的肽- hla结构的大型数据集，以及（iii）基于结构的筛选的新计算方法，可用于未来的研究中。我们的研究扩大了可能参与T细胞与sars - cov -2衍生肽交叉反应的卡介苗肽的列表，并确定了多个高密度的交叉反应肽“邻域”，这些“邻域”可能驱动卡介苗接种诱导的异源免疫，从而为未来的疫苗开发工作提供见解。
Although not being the first viral pandemic to affect humankind, we are now for the first time faced with a pandemic caused by a coronavirus. The Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) has been responsible for the COVID-19 pandemic, which caused more than 4.5 million deaths worldwide. Despite unprecedented efforts, with vaccines being developed in a record time, SARS-CoV-2 continues to spread worldwide with new variants arising in different countries. Such persistent spread is in part enabled by public resistance to vaccination in some countries, and limited access to vaccines in other countries. The limited vaccination coverage, the continued risk for resistant variants, and the existence of natural reservoirs for coronaviruses, highlight the importance of developing additional therapeutic strategies against SARS-CoV-2 and other coronaviruses. At the beginning of the pandemic it was suggested that countries with Bacillus Calmette-Guérin (BCG) vaccination programs could be associated with a reduced number and/or severity of COVID-19 cases. Preliminary studies have provided evidence for this relationship and further investigation is being conducted in ongoing clinical trials. The protection against SARS-CoV-2 induced by BCG vaccination may be mediated by cross-reactive T cell lymphocytes, which recognize peptides displayed by class I Human Leukocyte Antigens (HLA-I) on the surface of infected cells. In order to identify potential targets of T cell cross-reactivity, we implemented an in silico strategy combining sequence-based and structure-based methods to screen over 13,5 million possible cross-reactive peptide pairs from BCG and SARS-CoV-2. Our study produced (i) a list of immunogenic BCG-derived peptides that may prime T cell cross-reactivity against SARS-CoV-2, (ii) a large dataset of modeled peptide-HLA structures for the screened targets, and (iii) new computational methods for structure-based screenings that can be used by others in future studies. Our study expands the list of BCG peptides potentially involved in T cell cross-reactivity with SARS-CoV-2-derived peptides, and identifies multiple high-density “neighborhoods” of cross-reactive peptides which could be driving heterologous immunity induced by BCG vaccination, therefore providing insights for future vaccine development efforts.
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影响因子：
7.3
作者：
Eggenhuizen PJ;Ng BH;Chang J;Fell AL;Cheong RMY;Wong WY;Gan PY;Holdsworth SR;Ooi JD
通讯作者：
Ooi JD
影响因子：
64.5
作者：
Birnbaum ME;Mendoza JL;Sethi DK;Dong S;Glanville J;Dobbins J;Ozkan E;Davis MM;Wucherpfennig KW;Garcia KC
通讯作者：
Garcia KC
影响因子：
4.6
作者：
Aksu, K.;Naziroglu, T.;Ozkan, P.
通讯作者：
Ozkan, P.
DOI：
10.1073/pnas.2008410117
发表时间：
2020-07-28
影响因子：
11.1
作者：
Escobar, Luis E.;Molina-Cruz, Alvaro;Barillas-Mury, Carolina
通讯作者：
Barillas-Mury, Carolina
影响因子：
8
作者：
Barquera, Rodrigo;Collen, Evelyn;Sanchez-Mazas, Alicia
通讯作者：
Sanchez-Mazas, Alicia