Introduction of neutralizing immunogenicity index to the rational design of MERS coronavirus subunit vaccines

Lanying Du, Wanbo Tai, Yang Yang, Guangyu Zhao, Qing Zhu, Shihui Sun, Chang Liu, Xinrong Tao, Chien Te K. Tseng, Stanley Perlman, Shibo Jiang, Yusen Zhou, Fang Li

Research output: Contribution to journalArticlepeer-review

62 Scopus citations

Abstract

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.

Original languageEnglish (US)
Article number13473
JournalNature communications
Volume7
DOIs
StatePublished - Nov 22 2016

Bibliographical note

Funding Information:
This work was supported by NIH grants R01AI089728 and R01AI110700 (F.L.), NIH grant PO1AI060699 (S.P.), NIH grants R01AI098775, U01AI124260, R21AI109094 and the intramural fund of New York Blood Center NYB000348 (L.D. and S.J.), NIH grant R21AI113206-01 and pilot grants from the Center for Biodefense and Emerging Infectious Diseases and from the Galveston National Laboratory (C.K.T), China National

Publisher Copyright:
© 2016 The Author(s).

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