๐ Introduction of neutralizing immunogenicity index to the rational design of MERS coronavirus subunit vaccines
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.
keywords
๐ receptor-binding domain (99)
๐ immune response (314)
๐ immune responses (142)
๐ transgenic mice (28)
author
๐ค Du, Lanying
๐ค Tai, Wanbo
๐ค Yang, Yang
๐ค Zhao, Guangyu
๐ค Zhu, Qing
๐ค Sun, Shihui
๐ค Liu, Chang
๐ค Tao, Xinrong
๐ค Tseng, Chien Te K.
๐ค Perlman, Stanley
๐ค Jiang, Shibo
๐ค Zhou, Yusen
๐ค Li, Fang
year
โฐ 2016
journal
๐ Nature Communications
issn
๐ 20411723
volume
7
number
page
citedbycount
31
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