MersV1, Main, Exploration, bibRecord, 001192

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

Identifieur interne : 001192 ( Main/Exploration ); précédent : 001191; suivant : 001193

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

Auteurs : Lanying Du [États-Unis] ; Wanbo Tai [États-Unis, République populaire de Chine] ; Yang Yang ; Guangyu Zhao [République populaire de Chine] ; Qing Zhu [République populaire de Chine] ; Shihui Sun [République populaire de Chine] ; Chang Liu ; Xinrong Tao ; Chien-Te K. Tseng ; Stanley Perlman ; Shibo Jiang [États-Unis, République populaire de Chine] ; Yusen Zhou [République populaire de Chine] ; Fang Li

Source :

Nature Communications [ 2041-1723 ] ; 2016.

RBID : PMC:5121417

Descripteurs français

English descriptors

KwdEn :
- Animals, Antibodies, Neutralizing (immunology), Antibodies, Viral (immunology), Coronavirus Infections (prevention & control), HEK293 Cells, Humans, Mice, Mice, Inbred BALB C, Middle East Respiratory Syndrome Coronavirus (immunology), Protein Subunits (immunology), Recombinant Proteins (immunology), Spike Glycoprotein, Coronavirus (immunology), Spike Glycoprotein, Coronavirus (metabolism), Vaccines, Subunit (immunology), Viral Vaccines (immunology).
MESH :
- chemical , immunology : Antibodies, Neutralizing, Antibodies, Viral, Protein Subunits, Recombinant Proteins, Spike Glycoprotein, Coronavirus, Vaccines, Subunit, Viral Vaccines.
- immunology : Middle East Respiratory Syndrome Coronavirus.
- chemical , metabolism : Spike Glycoprotein, Coronavirus.
- prevention & control : Coronavirus Infections.
- Animals, HEK293 Cells, Humans, Mice, Mice, Inbred BALB C.

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.

Supplementary information

The online version of this article (doi:10.1038/ncomms13473) contains supplementary material, which is available to authorized users.

Url:

http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5121417

DOI: 10.1038/ncomms13473
PubMed: 27874853
PubMed Central: 5121417

Affiliations:

Le document en format XML

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<term>Antibodies, Neutralizing (immunology)</term>
<term>Antibodies, Viral (immunology)</term>
<term>Coronavirus Infections (prevention & control)</term>
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<term>Humans</term>
<term>Mice</term>
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<front><div type="abstract" xml:lang="en"><p id="Par1">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.</p>
<sec><title>Supplementary information</title>
<p>The online version of this article (doi:10.1038/ncomms13473) contains supplementary material, which is available to authorized users.</p>
</sec>
</div>
</front>
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Serveur d'exploration MERS

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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