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 Tseng, Stanley Perlman, Shibo Jiang, Yusen Zhou, Fang Li

Research output: Contribution to journalArticle

25 Citations (Scopus)

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

Fingerprint

vaccines
Coronavirus
Subunit Vaccines
Epitopes
Vaccines
combat
viruses
Viral Vaccines
masking
mice
masks
Masks
Viruses
Transgenic Mice
Polysaccharides
probes

ASJC Scopus subject areas

  • Chemistry(all)
  • Biochemistry, Genetics and Molecular Biology(all)
  • Physics and Astronomy(all)

Cite this

Introduction of neutralizing immunogenicity index to the rational design of MERS coronavirus subunit vaccines. / Du, Lanying; Tai, Wanbo; Yang, Yang; Zhao, Guangyu; Zhu, Qing; Sun, Shihui; Liu, Chang; Tao, Xinrong; Tseng, Chien-Te; Perlman, Stanley; Jiang, Shibo; Zhou, Yusen; Li, Fang.

In: Nature Communications, Vol. 7, 13473, 22.11.2016.

Research output: Contribution to journalArticle

Du, L, Tai, W, Yang, Y, Zhao, G, Zhu, Q, Sun, S, Liu, C, Tao, X, Tseng, C-T, Perlman, S, Jiang, S, Zhou, Y & Li, F 2016, 'Introduction of neutralizing immunogenicity index to the rational design of MERS coronavirus subunit vaccines', Nature Communications, vol. 7, 13473. https://doi.org/10.1038/ncomms13473
Du, Lanying ; Tai, Wanbo ; Yang, Yang ; Zhao, Guangyu ; Zhu, Qing ; Sun, Shihui ; Liu, Chang ; Tao, Xinrong ; Tseng, Chien-Te ; Perlman, Stanley ; Jiang, Shibo ; Zhou, Yusen ; Li, Fang. / Introduction of neutralizing immunogenicity index to the rational design of MERS coronavirus subunit vaccines. In: Nature Communications. 2016 ; Vol. 7.
@article{025e16ad86ad4c6686b951507e165460,
title = "Introduction of neutralizing immunogenicity index to the rational design of MERS coronavirus subunit vaccines",
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.",
author = "Lanying Du and Wanbo Tai and Yang Yang and Guangyu Zhao and Qing Zhu and Shihui Sun and Chang Liu and Xinrong Tao and Chien-Te Tseng and Stanley Perlman and Shibo Jiang and Yusen Zhou and Fang Li",
year = "2016",
month = "11",
day = "22",
doi = "10.1038/ncomms13473",
language = "English (US)",
volume = "7",
journal = "Nature Communications",
issn = "2041-1723",
publisher = "Nature Publishing Group",

}

TY - JOUR

T1 - Introduction of neutralizing immunogenicity index to the rational design of MERS coronavirus subunit vaccines

AU - Du, Lanying

AU - Tai, Wanbo

AU - Yang, Yang

AU - Zhao, Guangyu

AU - Zhu, Qing

AU - Sun, Shihui

AU - Liu, Chang

AU - Tao, Xinrong

AU - Tseng, Chien-Te

AU - Perlman, Stanley

AU - Jiang, Shibo

AU - Zhou, Yusen

AU - Li, Fang

PY - 2016/11/22

Y1 - 2016/11/22

N2 - 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.

AB - 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.

UR - http://www.scopus.com/inward/record.url?scp=84996844201&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=84996844201&partnerID=8YFLogxK

U2 - 10.1038/ncomms13473

DO - 10.1038/ncomms13473

M3 - Article

VL - 7

JO - Nature Communications

JF - Nature Communications

SN - 2041-1723

M1 - 13473

ER -