In silico design of a Zika virus non-structural protein 5 aiming vaccine protection against zika and dengue in different human populations.
In silico design of a Zika virus non-structural protein 5 aiming vaccine protection against zika and dengue in different human populations.
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DOI：
10.1186/s12929-017-0395-z
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发表时间：
2017-11-23
影响因子：
11
通讯作者：
Amorim JH
中科院分区：
文献类型：
--
作者：
Dos Santos Franco L;Oliveira Vidal P;Amorim JH
虫媒病毒寨卡病毒(ZIKV)和登革病毒(DENV)在巴西和世界其他热带地区具有重要的流行病学影响。最近，研究表明，先前对DENV的体液免疫在体外增强了ZIKV的复制，这可能导致更严重的疾病形式。因此，旨在通过中和抗体控制病毒感染的传统疫苗开发方法可能会诱导交叉反应增强抗体。相反，细胞免疫反应被证明能够独立于抗体控制DENV感染。本研究的目的是设计一种能够诱导针对DENV和ZIKV的细胞免疫反应的黄病毒NS5蛋白。设计了ZIKV NS5蛋白在不同大洲分离株中的一致序列。预测了巴西人群中最流行的I类和II类等位基因的表位。然后，对这些表位的保守性、种群覆盖率和沿整个抗原的分布进行了分析。选择了19个反应性较强的表位(百分位数为1)，并在ZIKV和DENV血清型之间100%保守。在三维模型上显示了这些表位沿蛋白质的分布，并计算了世界不同地区的种群覆盖率。预测设计的蛋白质是稳定的，所选的表位沿域分布是均匀的。在世界大部分热带地区，选定表位的人口覆盖率高于50%。这些结果表明，所提出的抗原具有在世界不同人群中诱导对ZIKV和DENV的保护性细胞免疫反应的潜力。本文的在线版本(10.1186/s129290170395-z)包含补充材料，授权用户可以使用。
The arboviruses Zika virus (ZIKV) and Dengue virus (DENV) have important epidemiological impact in Brazil and other tropical regions of the world. Recently, it was shown that previous humoral immunity to DENV enhances ZIKV replication in vitro, which may lead to more severe forms of the disease. Thus, traditional approaches of vaccine development aiming to control viral infection through neutralizing antibodies may induce cross-reactive enhancing antibodies. In contrast, cellular immune response was shown to be capable of controlling DENV infection independently of antibodies. The aim of the present study was to design a flavivirus NS5 protein capable of inducing a cellular immune response against DENV and ZIKV. A consensus sequence of ZIKV NS5 protein was designed among isolates from various continents. Epitopes were predicted for the most prevalent alleles of class I and II HLA in the Brazilian population. Then, this epitopes were analyzed with regard to their conservation, population coverage and distribution along the whole antigen. Nineteen epitopes predicted to be more reactive (percentile rank <1) and 100% conserved among ZIKV and DENV serotypes were selected. The distribution of such epitopes along the protein was shown on a three-dimensional model and population coverage was calculated for different regions of the world. The designed protein was predicted to be stable and the distribution of selected epitopes was shown to be homogeneous along domains. The population coverage of selected epitopes was higher than 50% for most of tropical areas of the world. Such results indicate that the proposed antigen has the potential to induce protective cellular immune response to ZIKV and DENV in different human populations of the world. The online version of this article (10.1186/s12929-017-0395-z) contains supplementary material, which is available to authorized users.
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影响因子：
30.5
作者：
Dejnirattisai W;Supasa P;Wongwiwat W;Rouvinski A;Barba-Spaeth G;Duangchinda T;Sakuntabhai A;Cao-Lormeau VM;Malasit P;Rey FA;Mongkolsapaya J;Screaton GR
通讯作者：
Screaton GR
影响因子：
158.5
作者：
Hadinegoro, S. R.;Arredondo-Garcia, J. L.;Saville, M.
通讯作者：
Saville, M.
DOI：
10.1073/pnas.1607931113
发表时间：
2016-07-12
影响因子：
11.1
作者：
Priyamvada, Lalita;Quicke, Kendra M.;Wrammert, Jens
通讯作者：
Wrammert, Jens
影响因子：
3.7
作者：
Amorim, Jaime Henrique;dos Santos Alves, Rubens Prince;de Souza Ferreira, Luis Carlos
通讯作者：
de Souza Ferreira, Luis Carlos
影响因子：
16.6
作者：
Zhao B;Zhang L;Zhen D;Yoo S;Ding Y;Chen D;Chen Y;Zhang Q;Doyle B;Xiong X;Liu M
通讯作者：
Liu M