MersV1, PubMed, Checkpoint, bibRecord, 001041

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

Identifieur interne : 001041 ( PubMed/Checkpoint ); précédent : 001040; suivant : 001042

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

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

Source :

Nature communications [ 2041-1723 ] ; 2016.

RBID : pubmed:27874853

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.

DOI: 10.1038/ncomms13473
PubMed: 27874853

Affiliations:

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<front><div type="abstract" xml:lang="en">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.</div>
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<Abstract><AbstractText>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.</AbstractText>
</Abstract>
<AuthorList CompleteYN="Y"><Author ValidYN="Y"><LastName>Du</LastName>
<ForeName>Lanying</ForeName>
<Initials>L</Initials>
<AffiliationInfo><Affiliation>Laboratory of Viral Immunology, Lindsley F. Kimball Research Institute, New York Blood Center, New York, New York 10065, USA.</Affiliation>
</AffiliationInfo>
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<AffiliationInfo><Affiliation>Laboratory of Viral Immunology, Lindsley F. Kimball Research Institute, New York Blood Center, New York, New York 10065, USA.</Affiliation>
</AffiliationInfo>
<AffiliationInfo><Affiliation>State Key Laboratory of Pathogen and Biosecurity, Beijing Institute of Microbiology and Epidemiology, Beijing 100071, China.</Affiliation>
</AffiliationInfo>
</Author>
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<Initials>Y</Initials>
<AffiliationInfo><Affiliation>Department of Pharmacology, University of Minnesota Medical School, Minneapolis, Minnesota 55455, USA.</Affiliation>
</AffiliationInfo>
</Author>
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<ForeName>Guangyu</ForeName>
<Initials>G</Initials>
<AffiliationInfo><Affiliation>State Key Laboratory of Pathogen and Biosecurity, Beijing Institute of Microbiology and Epidemiology, Beijing 100071, China.</Affiliation>
</AffiliationInfo>
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<ForeName>Qing</ForeName>
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<AffiliationInfo><Affiliation>State Key Laboratory of Pathogen and Biosecurity, Beijing Institute of Microbiology and Epidemiology, Beijing 100071, China.</Affiliation>
</AffiliationInfo>
</Author>
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<ForeName>Shihui</ForeName>
<Initials>S</Initials>
<AffiliationInfo><Affiliation>State Key Laboratory of Pathogen and Biosecurity, Beijing Institute of Microbiology and Epidemiology, Beijing 100071, China.</Affiliation>
</AffiliationInfo>
</Author>
<Author ValidYN="Y"><LastName>Liu</LastName>
<ForeName>Chang</ForeName>
<Initials>C</Initials>
<AffiliationInfo><Affiliation>Department of Pharmacology, University of Minnesota Medical School, Minneapolis, Minnesota 55455, USA.</Affiliation>
</AffiliationInfo>
</Author>
<Author ValidYN="Y"><LastName>Tao</LastName>
<ForeName>Xinrong</ForeName>
<Initials>X</Initials>
<AffiliationInfo><Affiliation>Department of Microbiology and Immunology and Center for Biodefense and Emerging Disease, University of Texas Medical Branch, Galveston, Texas 77555, USA.</Affiliation>
</AffiliationInfo>
</Author>
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<Initials>CK</Initials>
<AffiliationInfo><Affiliation>Department of Microbiology and Immunology and Center for Biodefense and Emerging Disease, University of Texas Medical Branch, Galveston, Texas 77555, USA.</Affiliation>
</AffiliationInfo>
</Author>
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<Initials>S</Initials>
<AffiliationInfo><Affiliation>Department of Microbiology, University of Iowa, Iowa City, Iowa 52242, USA.</Affiliation>
</AffiliationInfo>
</Author>
<Author ValidYN="Y"><LastName>Jiang</LastName>
<ForeName>Shibo</ForeName>
<Initials>S</Initials>
<AffiliationInfo><Affiliation>Laboratory of Viral Immunology, Lindsley F. Kimball Research Institute, New York Blood Center, New York, New York 10065, USA.</Affiliation>
</AffiliationInfo>
<AffiliationInfo><Affiliation>Key Laboratory of Medical Molecular Virology of Ministries of Education and Health, Shanghai Medical College and Institute of Medical Microbiology, Fudan University, Shanghai 200032, China.</Affiliation>
</AffiliationInfo>
</Author>
<Author ValidYN="Y"><LastName>Zhou</LastName>
<ForeName>Yusen</ForeName>
<Initials>Y</Initials>
<AffiliationInfo><Affiliation>State Key Laboratory of Pathogen and Biosecurity, Beijing Institute of Microbiology and Epidemiology, Beijing 100071, China.</Affiliation>
</AffiliationInfo>
</Author>
<Author ValidYN="Y"><LastName>Li</LastName>
<ForeName>Fang</ForeName>
<Initials>F</Initials>
<AffiliationInfo><Affiliation>Department of Pharmacology, University of Minnesota Medical School, Minneapolis, Minnesota 55455, USA.</Affiliation>
</AffiliationInfo>
</Author>
</AuthorList>
<Language>eng</Language>
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<Acronym>AI</Acronym>
<Agency>NIAID NIH HHS</Agency>
<Country>United States</Country>
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<Agency>NIAID NIH HHS</Agency>
<Country>United States</Country>
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<Acronym>AI</Acronym>
<Agency>NIAID NIH HHS</Agency>
<Country>United States</Country>
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<PublicationType UI="D052060">Research Support, N.I.H., Intramural</PublicationType>
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<ArticleDate DateType="Electronic"><Year>2016</Year>
<Month>11</Month>
<Day>22</Day>
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<MedlineJournalInfo><Country>England</Country>
<MedlineTA>Nat Commun</MedlineTA>
<NlmUniqueID>101528555</NlmUniqueID>
<ISSNLinking>2041-1723</ISSNLinking>
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<affiliations><list><country><li>République populaire de Chine</li>
<li>États-Unis</li>
</country>
<region><li>Iowa</li>
</region>
<settlement><li>Iowa City</li>
<li>Pékin</li>
</settlement>
<orgName><li>Université de l'Iowa</li>
</orgName>
</list>
<tree><country name="États-Unis"><noRegion><name sortKey="Du, Lanying" sort="Du, Lanying" uniqKey="Du L" first="Lanying" last="Du">Lanying Du</name>
</noRegion>
<name sortKey="Jiang, Shibo" sort="Jiang, Shibo" uniqKey="Jiang S" first="Shibo" last="Jiang">Shibo Jiang</name>
<name sortKey="Li, Fang" sort="Li, Fang" uniqKey="Li F" first="Fang" last="Li">Fang Li</name>
<name sortKey="Liu, Chang" sort="Liu, Chang" uniqKey="Liu C" first="Chang" last="Liu">Chang Liu</name>
<name sortKey="Perlman, Stanley" sort="Perlman, Stanley" uniqKey="Perlman S" first="Stanley" last="Perlman">Stanley Perlman</name>
<name sortKey="Tai, Wanbo" sort="Tai, Wanbo" uniqKey="Tai W" first="Wanbo" last="Tai">Wanbo Tai</name>
<name sortKey="Tao, Xinrong" sort="Tao, Xinrong" uniqKey="Tao X" first="Xinrong" last="Tao">Xinrong Tao</name>
<name sortKey="Tseng, Chien Te K" sort="Tseng, Chien Te K" uniqKey="Tseng C" first="Chien-Te K" last="Tseng">Chien-Te K. Tseng</name>
<name sortKey="Yang, Yang" sort="Yang, Yang" uniqKey="Yang Y" first="Yang" last="Yang">Yang Yang</name>
</country>
<country name="République populaire de Chine"><noRegion><name sortKey="Zhao, Guangyu" sort="Zhao, Guangyu" uniqKey="Zhao G" first="Guangyu" last="Zhao">Guangyu Zhao</name>
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<name sortKey="Sun, Shihui" sort="Sun, Shihui" uniqKey="Sun S" first="Shihui" last="Sun">Shihui Sun</name>
<name sortKey="Zhou, Yusen" sort="Zhou, Yusen" uniqKey="Zhou Y" first="Yusen" last="Zhou">Yusen Zhou</name>
<name sortKey="Zhu, Qing" sort="Zhu, Qing" uniqKey="Zhu Q" first="Qing" last="Zhu">Qing Zhu</name>
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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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