Serveur d'exploration MERS

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Epitope-Based Vaccine Target Screening against Highly Pathogenic MERS-CoV: An In Silico Approach Applied to Emerging Infectious Diseases

Identifieur interne : 001805 ( Main/Exploration ); précédent : 001804; suivant : 001806

Epitope-Based Vaccine Target Screening against Highly Pathogenic MERS-CoV: An In Silico Approach Applied to Emerging Infectious Diseases

Auteurs : Jiandong Shi [République populaire de Chine] ; Jing Zhang [République populaire de Chine] ; Sijin Li [République populaire de Chine] ; Jing Sun [République populaire de Chine] ; Yumei Teng [République populaire de Chine] ; Meini Wu [République populaire de Chine] ; Jianfan Li [République populaire de Chine] ; Yanhan Li [République populaire de Chine] ; Ningzhu Hu [République populaire de Chine] ; Haixuan Wang [République populaire de Chine] ; Yunzhang Hu [République populaire de Chine]

Source :

RBID : PMC:4671582

Descripteurs français

English descriptors

Abstract

Middle East respiratory syndrome coronavirus (MERS-CoV) with pandemic potential is a major worldwide threat to public health. However, vaccine development for this pathogen lags behind as immunity associated with protection is currently largely unknown. In this study, an immunoinformatics-driven genome-wide screening strategy of vaccine targets was performed to thoroughly screen the vital and effective dominant immunogens against MERS-CoV. Conservancy and population coverage analysis of the epitopes were done by the Immune Epitope Database. The results showed that the nucleocapsid (N) protein of MERS-CoV might be a better protective immunogen with high conservancy and potential eliciting both neutralizing antibodies and T-cell responses compared with spike (S) protein. Further, the B-cell, helper T-cell and cytotoxic T lymphocyte (CTL) epitopes were screened and mapped to the N protein. A total of 15 linear and 10 conformal B-cell epitopes that may induce protective neutralizing antibodies were obtained. Additionally, a total of 71 peptides with 9-mer core sequence were identified as helper T-cell epitopes, and 34 peptides were identified as CTL epitopes. Based on the maximum HLA binding alleles, top 10 helper T-cell epitopes and CTL epitopes that may elicit protective cellular immune responses against MERS-CoV were selected as MERS vaccine candidates. Population coverage analysis showed that the putative helper T-cell epitopes and CTL epitopes could cover the vast majority of the population in 15 geographic regions considered where vaccine would be employed. The B- and T-cell stimulation potentials of the screened epitopes is to be further validated for their efficient use as vaccines against MERS-CoV. Collectively, this study provides novel vaccine target candidates and may prompt further development of vaccines against MERS-CoV and other emerging infectious diseases.


Url:
DOI: 10.1371/journal.pone.0144475
PubMed: 26641892
PubMed Central: 4671582


Affiliations:


Links toward previous steps (curation, corpus...)


Le document en format XML

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<addr-line>Institute of Medical Biology, Chinese Academy of Medical Sciences and Peking Union Medical College, Kunming, China</addr-line>
</nlm:aff>
<country xml:lang="fr">République populaire de Chine</country>
<wicri:regionArea>Institute of Medical Biology, Chinese Academy of Medical Sciences and Peking Union Medical College, Kunming</wicri:regionArea>
<wicri:noRegion>Kunming</wicri:noRegion>
</affiliation>
<affiliation wicri:level="1">
<nlm:aff id="aff002">
<addr-line>Yunnan Provincial Key Laboratory of Arbo Infectious Disease Control Research (Preparing), Institute of Medical Biology, Chinese Academy of Medical Sciences, Kunming, China</addr-line>
</nlm:aff>
<country xml:lang="fr">République populaire de Chine</country>
<wicri:regionArea>Yunnan Provincial Key Laboratory of Arbo Infectious Disease Control Research (Preparing), Institute of Medical Biology, Chinese Academy of Medical Sciences, Kunming</wicri:regionArea>
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<author>
<name sortKey="Li, Yanhan" sort="Li, Yanhan" uniqKey="Li Y" first="Yanhan" last="Li">Yanhan Li</name>
<affiliation wicri:level="1">
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<addr-line>Institute of Medical Biology, Chinese Academy of Medical Sciences and Peking Union Medical College, Kunming, China</addr-line>
</nlm:aff>
<country xml:lang="fr">République populaire de Chine</country>
<wicri:regionArea>Institute of Medical Biology, Chinese Academy of Medical Sciences and Peking Union Medical College, Kunming</wicri:regionArea>
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<affiliation wicri:level="1">
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<addr-line>Yunnan Provincial Key Laboratory of Arbo Infectious Disease Control Research (Preparing), Institute of Medical Biology, Chinese Academy of Medical Sciences, Kunming, China</addr-line>
</nlm:aff>
<country xml:lang="fr">République populaire de Chine</country>
<wicri:regionArea>Yunnan Provincial Key Laboratory of Arbo Infectious Disease Control Research (Preparing), Institute of Medical Biology, Chinese Academy of Medical Sciences, Kunming</wicri:regionArea>
<wicri:noRegion>Kunming</wicri:noRegion>
</affiliation>
</author>
<author>
<name sortKey="Hu, Ningzhu" sort="Hu, Ningzhu" uniqKey="Hu N" first="Ningzhu" last="Hu">Ningzhu Hu</name>
<affiliation wicri:level="1">
<nlm:aff id="aff001">
<addr-line>Institute of Medical Biology, Chinese Academy of Medical Sciences and Peking Union Medical College, Kunming, China</addr-line>
</nlm:aff>
<country xml:lang="fr">République populaire de Chine</country>
<wicri:regionArea>Institute of Medical Biology, Chinese Academy of Medical Sciences and Peking Union Medical College, Kunming</wicri:regionArea>
<wicri:noRegion>Kunming</wicri:noRegion>
</affiliation>
<affiliation wicri:level="1">
<nlm:aff id="aff002">
<addr-line>Yunnan Provincial Key Laboratory of Arbo Infectious Disease Control Research (Preparing), Institute of Medical Biology, Chinese Academy of Medical Sciences, Kunming, China</addr-line>
</nlm:aff>
<country xml:lang="fr">République populaire de Chine</country>
<wicri:regionArea>Yunnan Provincial Key Laboratory of Arbo Infectious Disease Control Research (Preparing), Institute of Medical Biology, Chinese Academy of Medical Sciences, Kunming</wicri:regionArea>
<wicri:noRegion>Kunming</wicri:noRegion>
</affiliation>
</author>
<author>
<name sortKey="Wang, Haixuan" sort="Wang, Haixuan" uniqKey="Wang H" first="Haixuan" last="Wang">Haixuan Wang</name>
<affiliation wicri:level="1">
<nlm:aff id="aff001">
<addr-line>Institute of Medical Biology, Chinese Academy of Medical Sciences and Peking Union Medical College, Kunming, China</addr-line>
</nlm:aff>
<country xml:lang="fr">République populaire de Chine</country>
<wicri:regionArea>Institute of Medical Biology, Chinese Academy of Medical Sciences and Peking Union Medical College, Kunming</wicri:regionArea>
<wicri:noRegion>Kunming</wicri:noRegion>
</affiliation>
<affiliation wicri:level="1">
<nlm:aff id="aff002">
<addr-line>Yunnan Provincial Key Laboratory of Arbo Infectious Disease Control Research (Preparing), Institute of Medical Biology, Chinese Academy of Medical Sciences, Kunming, China</addr-line>
</nlm:aff>
<country xml:lang="fr">République populaire de Chine</country>
<wicri:regionArea>Yunnan Provincial Key Laboratory of Arbo Infectious Disease Control Research (Preparing), Institute of Medical Biology, Chinese Academy of Medical Sciences, Kunming</wicri:regionArea>
<wicri:noRegion>Kunming</wicri:noRegion>
</affiliation>
</author>
<author>
<name sortKey="Hu, Yunzhang" sort="Hu, Yunzhang" uniqKey="Hu Y" first="Yunzhang" last="Hu">Yunzhang Hu</name>
<affiliation wicri:level="1">
<nlm:aff id="aff001">
<addr-line>Institute of Medical Biology, Chinese Academy of Medical Sciences and Peking Union Medical College, Kunming, China</addr-line>
</nlm:aff>
<country xml:lang="fr">République populaire de Chine</country>
<wicri:regionArea>Institute of Medical Biology, Chinese Academy of Medical Sciences and Peking Union Medical College, Kunming</wicri:regionArea>
<wicri:noRegion>Kunming</wicri:noRegion>
</affiliation>
<affiliation wicri:level="1">
<nlm:aff id="aff002">
<addr-line>Yunnan Provincial Key Laboratory of Arbo Infectious Disease Control Research (Preparing), Institute of Medical Biology, Chinese Academy of Medical Sciences, Kunming, China</addr-line>
</nlm:aff>
<country xml:lang="fr">République populaire de Chine</country>
<wicri:regionArea>Yunnan Provincial Key Laboratory of Arbo Infectious Disease Control Research (Preparing), Institute of Medical Biology, Chinese Academy of Medical Sciences, Kunming</wicri:regionArea>
<wicri:noRegion>Kunming</wicri:noRegion>
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</author>
</analytic>
<series>
<title level="j">PLoS ONE</title>
<idno type="eISSN">1932-6203</idno>
<imprint>
<date when="2015">2015</date>
</imprint>
</series>
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<profileDesc>
<textClass>
<keywords scheme="KwdEn" xml:lang="en">
<term>Antibodies, Neutralizing (immunology)</term>
<term>Coronavirus Infections (immunology)</term>
<term>Coronavirus Infections (virology)</term>
<term>Epitopes, B-Lymphocyte (immunology)</term>
<term>Epitopes, T-Lymphocyte (immunology)</term>
<term>Humans</term>
<term>Immunity, Cellular (immunology)</term>
<term>Middle East Respiratory Syndrome Coronavirus (immunology)</term>
<term>Nucleocapsid Proteins (immunology)</term>
<term>Spike Glycoprotein, Coronavirus (immunology)</term>
<term>T-Lymphocytes, Helper-Inducer (immunology)</term>
<term>Viral Vaccines (immunology)</term>
</keywords>
<keywords scheme="KwdFr" xml:lang="fr">
<term>Anticorps neutralisants (immunologie)</term>
<term>Coronavirus du syndrome respiratoire du Moyen-Orient (immunologie)</term>
<term>Déterminants antigéniques des lymphocytes B (immunologie)</term>
<term>Déterminants antigéniques des lymphocytes T (immunologie)</term>
<term>Glycoprotéine de spicule des coronavirus (immunologie)</term>
<term>Humains</term>
<term>Immunité cellulaire (immunologie)</term>
<term>Infections à coronavirus (immunologie)</term>
<term>Infections à coronavirus (virologie)</term>
<term>Lymphocytes T auxiliaires (immunologie)</term>
<term>Protéines nucléocapside (immunologie)</term>
<term>Vaccins antiviraux (immunologie)</term>
</keywords>
<keywords scheme="MESH" type="chemical" qualifier="immunology" xml:lang="en">
<term>Antibodies, Neutralizing</term>
<term>Epitopes, B-Lymphocyte</term>
<term>Epitopes, T-Lymphocyte</term>
<term>Nucleocapsid Proteins</term>
<term>Spike Glycoprotein, Coronavirus</term>
<term>Viral Vaccines</term>
</keywords>
<keywords scheme="MESH" qualifier="immunologie" xml:lang="fr">
<term>Anticorps neutralisants</term>
<term>Coronavirus du syndrome respiratoire du Moyen-Orient</term>
<term>Déterminants antigéniques des lymphocytes B</term>
<term>Déterminants antigéniques des lymphocytes T</term>
<term>Glycoprotéine de spicule des coronavirus</term>
<term>Immunité cellulaire</term>
<term>Infections à coronavirus</term>
<term>Lymphocytes T auxiliaires</term>
<term>Protéines nucléocapside</term>
<term>Vaccins antiviraux</term>
</keywords>
<keywords scheme="MESH" qualifier="immunology" xml:lang="en">
<term>Coronavirus Infections</term>
<term>Immunity, Cellular</term>
<term>Middle East Respiratory Syndrome Coronavirus</term>
<term>T-Lymphocytes, Helper-Inducer</term>
</keywords>
<keywords scheme="MESH" qualifier="virologie" xml:lang="fr">
<term>Infections à coronavirus</term>
</keywords>
<keywords scheme="MESH" qualifier="virology" xml:lang="en">
<term>Coronavirus Infections</term>
</keywords>
<keywords scheme="MESH" xml:lang="en">
<term>Humans</term>
</keywords>
<keywords scheme="MESH" xml:lang="fr">
<term>Humains</term>
</keywords>
</textClass>
</profileDesc>
</teiHeader>
<front>
<div type="abstract" xml:lang="en">
<p>Middle East respiratory syndrome coronavirus (MERS-CoV) with pandemic potential is a major worldwide threat to public health. However, vaccine development for this pathogen lags behind as immunity associated with protection is currently largely unknown. In this study, an immunoinformatics-driven genome-wide screening strategy of vaccine targets was performed to thoroughly screen the vital and effective dominant immunogens against MERS-CoV. Conservancy and population coverage analysis of the epitopes were done by the Immune Epitope Database. The results showed that the nucleocapsid (N) protein of MERS-CoV might be a better protective immunogen with high conservancy and potential eliciting both neutralizing antibodies and T-cell responses compared with spike (S) protein. Further, the B-cell, helper T-cell and cytotoxic T lymphocyte (CTL) epitopes were screened and mapped to the N protein. A total of 15 linear and 10 conformal B-cell epitopes that may induce protective neutralizing antibodies were obtained. Additionally, a total of 71 peptides with 9-mer core sequence were identified as helper T-cell epitopes, and 34 peptides were identified as CTL epitopes. Based on the maximum HLA binding alleles, top 10 helper T-cell epitopes and CTL epitopes that may elicit protective cellular immune responses against MERS-CoV were selected as MERS vaccine candidates. Population coverage analysis showed that the putative helper T-cell epitopes and CTL epitopes could cover the vast majority of the population in 15 geographic regions considered where vaccine would be employed. The B- and T-cell stimulation potentials of the screened epitopes is to be further validated for their efficient use as vaccines against MERS-CoV. Collectively, this study provides novel vaccine target candidates and may prompt further development of vaccines against MERS-CoV and other emerging infectious diseases.</p>
</div>
</front>
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<li>République populaire de Chine</li>
</country>
</list>
<tree>
<country name="République populaire de Chine">
<noRegion>
<name sortKey="Shi, Jiandong" sort="Shi, Jiandong" uniqKey="Shi J" first="Jiandong" last="Shi">Jiandong Shi</name>
</noRegion>
<name sortKey="Hu, Ningzhu" sort="Hu, Ningzhu" uniqKey="Hu N" first="Ningzhu" last="Hu">Ningzhu Hu</name>
<name sortKey="Hu, Ningzhu" sort="Hu, Ningzhu" uniqKey="Hu N" first="Ningzhu" last="Hu">Ningzhu Hu</name>
<name sortKey="Hu, Yunzhang" sort="Hu, Yunzhang" uniqKey="Hu Y" first="Yunzhang" last="Hu">Yunzhang Hu</name>
<name sortKey="Hu, Yunzhang" sort="Hu, Yunzhang" uniqKey="Hu Y" first="Yunzhang" last="Hu">Yunzhang Hu</name>
<name sortKey="Li, Jianfan" sort="Li, Jianfan" uniqKey="Li J" first="Jianfan" last="Li">Jianfan Li</name>
<name sortKey="Li, Jianfan" sort="Li, Jianfan" uniqKey="Li J" first="Jianfan" last="Li">Jianfan Li</name>
<name sortKey="Li, Sijin" sort="Li, Sijin" uniqKey="Li S" first="Sijin" last="Li">Sijin Li</name>
<name sortKey="Li, Sijin" sort="Li, Sijin" uniqKey="Li S" first="Sijin" last="Li">Sijin Li</name>
<name sortKey="Li, Yanhan" sort="Li, Yanhan" uniqKey="Li Y" first="Yanhan" last="Li">Yanhan Li</name>
<name sortKey="Li, Yanhan" sort="Li, Yanhan" uniqKey="Li Y" first="Yanhan" last="Li">Yanhan Li</name>
<name sortKey="Shi, Jiandong" sort="Shi, Jiandong" uniqKey="Shi J" first="Jiandong" last="Shi">Jiandong Shi</name>
<name sortKey="Sun, Jing" sort="Sun, Jing" uniqKey="Sun J" first="Jing" last="Sun">Jing Sun</name>
<name sortKey="Sun, Jing" sort="Sun, Jing" uniqKey="Sun J" first="Jing" last="Sun">Jing Sun</name>
<name sortKey="Teng, Yumei" sort="Teng, Yumei" uniqKey="Teng Y" first="Yumei" last="Teng">Yumei Teng</name>
<name sortKey="Teng, Yumei" sort="Teng, Yumei" uniqKey="Teng Y" first="Yumei" last="Teng">Yumei Teng</name>
<name sortKey="Wang, Haixuan" sort="Wang, Haixuan" uniqKey="Wang H" first="Haixuan" last="Wang">Haixuan Wang</name>
<name sortKey="Wang, Haixuan" sort="Wang, Haixuan" uniqKey="Wang H" first="Haixuan" last="Wang">Haixuan Wang</name>
<name sortKey="Wu, Meini" sort="Wu, Meini" uniqKey="Wu M" first="Meini" last="Wu">Meini Wu</name>
<name sortKey="Wu, Meini" sort="Wu, Meini" uniqKey="Wu M" first="Meini" last="Wu">Meini Wu</name>
<name sortKey="Zhang, Jing" sort="Zhang, Jing" uniqKey="Zhang J" first="Jing" last="Zhang">Jing Zhang</name>
<name sortKey="Zhang, Jing" sort="Zhang, Jing" uniqKey="Zhang J" first="Jing" last="Zhang">Jing Zhang</name>
</country>
</tree>
</affiliations>
</record>

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