Introduction of neutralizing immunogenicity index to the rational design of MERS coronavirus subunit vaccines.
Introduction of neutralizing immunogenicity index to the rational design of MERS coronavirus subunit vaccines.
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DOI：
10.1038/ncomms13473
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发表时间：
2016-11-22
影响因子：
16.6
通讯作者：
Li, Fang
中科院分区：
文献类型：
--
作者：
Du, Lanying;Tai, Wanbo;Yang, Yang;Zhao, Guangyu;Zhu, Qing;Sun, Shihui;Liu, Chang;Tao, Xinrong;Tseng, Chien-Te K.;Perlman, Stanley;Jiang, Shibo;Zhou, Yusen;Li, Fang
病毒亚单位疫苗通常含有转移宿主免疫应答的免疫显性非中和表位。在疫苗设计中应消除这些表位，但没有可靠的方法来评估表位引发中和免疫应答的能力。本文提出了中和免疫原性指数（NII）的概念来评价表位的中和免疫原性。为了确定NII，我们用聚糖探针掩蔽表位，然后评估表位对疫苗的总体中和免疫原性的贡献。作为概念验证，我们测量了由MERS冠状病毒（MERS-CoV）受体结合结构域组成的免疫原上不同表位的NII。此外，我们通过掩蔽具有负NII评分的表位来设计该疫苗的变体形式。这种工程化疫苗在保护转基因小鼠免受致死MERS-CoV攻击方面表现出显著增强的功效。我们的研究可能会指导高效亚单位疫苗的合理设计，以对抗MERS-CoV和其他威胁生命的病毒。病毒亚单位疫苗含有引发非中和免疫应答的表位。在这里，Du等人用聚糖探针掩蔽了MERS冠状病毒亚单位疫苗上的免疫显性非中和表位，从而显著提高了疫苗的效力。
Viral subunit vaccines often contain immunodominant non-neutralizing epitopes that divert host immune responses. These epitopes should be eliminated in vaccine design, but there is no reliable method for evaluating an epitope's capacity to elicit neutralizing immune responses. Here we introduce a new concept ‘neutralizing immunogenicity index' (NII) to evaluate an epitope's neutralizing immunogenicity. To determine the NII, we mask the epitope with a glycan probe and then assess the epitope's contribution to the vaccine's overall neutralizing immunogenicity. As proof-of-concept, we measure the NII for different epitopes on an immunogen comprised of the receptor-binding domain from MERS coronavirus (MERS-CoV). Further, we design a variant form of this vaccine by masking an epitope that has a negative NII score. This engineered vaccine demonstrates significantly enhanced efficacy in protecting transgenic mice from lethal MERS-CoV challenge. Our study may guide the rational design of highly effective subunit vaccines to combat MERS-CoV and other life-threatening viruses. Viral subunit vaccines contain epitopes that elicit non-neutralizing immune responses. Here, Du et al. mask an immunodominant non-neutralizing epitope on a MERS coronavirus subunit vaccine with a glycan probe, leading to significantly improved efficacy of the vaccine.
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影响因子：
64.8
作者：
Li W;Moore MJ;Vasilieva N;Sui J;Wong SK;Berne MA;Somasundaran M;Sullivan JL;Luzuriaga K;Greenough TC;Choe H;Farzan M
通讯作者：
Farzan M
影响因子：
5.4
作者：
Du, Lanying;Zhao, Guangyu;Jiang, Shibo
通讯作者：
Jiang, Shibo
影响因子：
17.3
作者：
Dormitzer PR;Ulmer JB;Rappuoli R
通讯作者：
Rappuoli R
影响因子：
11.4
作者：
Kessler, J. H.;Bres-Vloemans, S. A.;Melief, C. J. M.
通讯作者：
Melief, C. J. M.
影响因子：
5.5
作者：
Ma, Cuiqing;Wang, Lili;Tao, Xinrong;Zhang, Naru;Yang, Yang;Tseng, Chien-Te K.;Li, Fang;Zhou, Yusen;Jiang, Shibo;Du, Lanying
通讯作者：
Du, Lanying