Serveur d'exploration MERS

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Single intranasal immunization with chimpanzee adenovirus-based vaccine induces sustained and protective immunity against MERS-CoV infection

Identifieur interne : 000383 ( Main/Exploration ); précédent : 000382; suivant : 000384

Single intranasal immunization with chimpanzee adenovirus-based vaccine induces sustained and protective immunity against MERS-CoV infection

Auteurs : Wenxu Jia [République populaire de Chine] ; Rudragouda Channappanavar [États-Unis] ; Chao Zhang [République populaire de Chine] ; Mingxi Li [République populaire de Chine] ; Haixia Zhou [République populaire de Chine] ; Shuyuan Zhang [République populaire de Chine] ; Panpan Zhou [République populaire de Chine] ; Jiuyang Xu [République populaire de Chine] ; Sisi Shan [République populaire de Chine] ; Xuanling Shi [République populaire de Chine] ; Xinquan Wang [République populaire de Chine] ; Jincun Zhao [République populaire de Chine] ; Dongming Zhou [République populaire de Chine] ; Stanley Perlman [États-Unis, République populaire de Chine] ; Linqi Zhang [République populaire de Chine]

Source :

RBID : PMC:6542157

Descripteurs français

English descriptors

Abstract

ABSTRACT

The recently identified Middle East Respiratory Syndrome Coronavirus (MERS-CoV) causes severe and fatal acute respiratory illness in humans. However, no approved prophylactic and therapeutic interventions are currently available. The MERS-CoV envelope spike protein serves as a crucial target for neutralizing antibodies and vaccine development, as it plays a critical role in mediating viral entry through interactions with the cellular receptor, dipeptidyl peptidase 4 (DPP4). Here, we constructed a recombinant rare serotype of the chimpanzee adenovirus 68 (AdC68) that expresses full-length MERS-CoV S protein (AdC68-S). Single intranasal immunization with AdC68-S induced robust and sustained neutralizing antibody and T cell responses in BALB/c mice. In a human DPP4 knock-in (hDPP4-KI) mouse model, it completely protected against lethal challenge with a mouse-adapted MERS-CoV (MERS-CoV-MA). Passive transfer of immune sera to naïve hDPP4-KI mice also provided survival advantages from lethal MERS-CoV-MA challenge. Analysis of sera absorption and isolated monoclonal antibodies from immunized mice demonstrated that the potent and broad neutralizing activity was largely attributed to antibodies targeting the receptor binding domain (RBD) of the S protein. These results show that AdC68-S can induce protective immune responses in mice and represent a promising candidate for further development against MERS-CoV infection in both dromedaries and humans.


Url:
DOI: 10.1080/22221751.2019.1620083
PubMed: 31130102
PubMed Central: 6542157


Affiliations:


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


Le document en format XML

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<title xml:lang="en" level="a" type="main">Single intranasal immunization with chimpanzee adenovirus-based vaccine induces sustained and protective immunity against MERS-CoV infection</title>
<author>
<name sortKey="Jia, Wenxu" sort="Jia, Wenxu" uniqKey="Jia W" first="Wenxu" last="Jia">Wenxu Jia</name>
<affiliation wicri:level="1">
<nlm:aff id="AF1">
<institution>Comprehensive AIDS Research Center, Collaborative Innovation Center for Diagnosis and Treatment of Infectious Diseases, Beijing Advanced Innovation Center for Structural Biology, Department of Basic Medical Sciences, School of Medicine, Tsinghua University</institution>
, Beijing,
<country>People’s Republic of China</country>
</nlm:aff>
<country xml:lang="fr">République populaire de Chine</country>
<wicri:regionArea># see nlm:aff country strict</wicri:regionArea>
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<name sortKey="Channappanavar, Rudragouda" sort="Channappanavar, Rudragouda" uniqKey="Channappanavar R" first="Rudragouda" last="Channappanavar">Rudragouda Channappanavar</name>
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<institution>Department of Microbiology and Immunology, The University of Iowa</institution>
, Iowa City, IA,
<country>USA</country>
</nlm:aff>
<country xml:lang="fr">États-Unis</country>
<wicri:regionArea># see nlm:aff country strict</wicri:regionArea>
</affiliation>
<affiliation wicri:level="1">
<nlm:aff id="AF3">
<institution>Department of Acute and Tertiary Care, and the Institute for the Study of Host–Pathogen Systems, University of Tennessee Health Science Center</institution>
, Memphis, TN,
<country>USA</country>
</nlm:aff>
<country xml:lang="fr">États-Unis</country>
<wicri:regionArea># see nlm:aff country strict</wicri:regionArea>
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<name sortKey="Zhang, Chao" sort="Zhang, Chao" uniqKey="Zhang C" first="Chao" last="Zhang">Chao Zhang</name>
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, Nanjing,
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</nlm:aff>
<country xml:lang="fr">République populaire de Chine</country>
<wicri:regionArea># see nlm:aff country strict</wicri:regionArea>
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, Shanghai,
<country>People’s Republic of China</country>
</nlm:aff>
<country xml:lang="fr">République populaire de Chine</country>
<wicri:regionArea># see nlm:aff country strict</wicri:regionArea>
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<name sortKey="Zhou, Haixia" sort="Zhou, Haixia" uniqKey="Zhou H" first="Haixia" last="Zhou">Haixia Zhou</name>
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<wicri:regionArea># see nlm:aff country strict</wicri:regionArea>
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<name sortKey="Zhang, Shuyuan" sort="Zhang, Shuyuan" uniqKey="Zhang S" first="Shuyuan" last="Zhang">Shuyuan Zhang</name>
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<wicri:regionArea># see nlm:aff country strict</wicri:regionArea>
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<name sortKey="Xu, Jiuyang" sort="Xu, Jiuyang" uniqKey="Xu J" first="Jiuyang" last="Xu">Jiuyang Xu</name>
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<country>People’s Republic of China</country>
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<wicri:regionArea># see nlm:aff country strict</wicri:regionArea>
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<name sortKey="Shan, Sisi" sort="Shan, Sisi" uniqKey="Shan S" first="Sisi" last="Shan">Sisi Shan</name>
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<institution>Comprehensive AIDS Research Center, Collaborative Innovation Center for Diagnosis and Treatment of Infectious Diseases, Beijing Advanced Innovation Center for Structural Biology, Department of Basic Medical Sciences, School of Medicine, Tsinghua University</institution>
, Beijing,
<country>People’s Republic of China</country>
</nlm:aff>
<country xml:lang="fr">République populaire de Chine</country>
<wicri:regionArea># see nlm:aff country strict</wicri:regionArea>
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<name sortKey="Shi, Xuanling" sort="Shi, Xuanling" uniqKey="Shi X" first="Xuanling" last="Shi">Xuanling Shi</name>
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<nlm:aff id="AF1">
<institution>Comprehensive AIDS Research Center, Collaborative Innovation Center for Diagnosis and Treatment of Infectious Diseases, Beijing Advanced Innovation Center for Structural Biology, Department of Basic Medical Sciences, School of Medicine, Tsinghua University</institution>
, Beijing,
<country>People’s Republic of China</country>
</nlm:aff>
<country xml:lang="fr">République populaire de Chine</country>
<wicri:regionArea># see nlm:aff country strict</wicri:regionArea>
</affiliation>
</author>
<author>
<name sortKey="Wang, Xinquan" sort="Wang, Xinquan" uniqKey="Wang X" first="Xinquan" last="Wang">Xinquan Wang</name>
<affiliation wicri:level="1">
<nlm:aff id="AF6">
<institution>The Ministry of Education Key Laboratory of Protein Science, Beijing Advanced Innovation Center for Structural Biology, Collaborative Innovation Center for Biotherapy, School of Life Sciences, Tsinghua University</institution>
, Beijing,
<country>People’s Republic of China</country>
</nlm:aff>
<country xml:lang="fr">République populaire de Chine</country>
<wicri:regionArea># see nlm:aff country strict</wicri:regionArea>
</affiliation>
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<author>
<name sortKey="Zhao, Jincun" sort="Zhao, Jincun" uniqKey="Zhao J" first="Jincun" last="Zhao">Jincun Zhao</name>
<affiliation wicri:level="1">
<nlm:aff id="AF7">
<institution>State Key Laboratory of Respiratory Disease, Guangzhou Institute of Respiratory Health, The First Affiliated Hospital of Guangzhou Medical University</institution>
, Guangzhou,
<country>People’s Republic of China</country>
</nlm:aff>
<country xml:lang="fr">République populaire de Chine</country>
<wicri:regionArea># see nlm:aff country strict</wicri:regionArea>
</affiliation>
</author>
<author>
<name sortKey="Zhou, Dongming" sort="Zhou, Dongming" uniqKey="Zhou D" first="Dongming" last="Zhou">Dongming Zhou</name>
<affiliation wicri:level="1">
<nlm:aff id="AF5">
<institution>Key Laboratory of Molecular Virology & Immunology, Vaccine Research Center, Institut Pasteur of Shanghai, Chinese Academy of Sciences</institution>
, Shanghai,
<country>People’s Republic of China</country>
</nlm:aff>
<country xml:lang="fr">République populaire de Chine</country>
<wicri:regionArea># see nlm:aff country strict</wicri:regionArea>
</affiliation>
</author>
<author>
<name sortKey="Perlman, Stanley" sort="Perlman, Stanley" uniqKey="Perlman S" first="Stanley" last="Perlman">Stanley Perlman</name>
<affiliation wicri:level="1">
<nlm:aff id="AF2">
<institution>Department of Microbiology and Immunology, The University of Iowa</institution>
, Iowa City, IA,
<country>USA</country>
</nlm:aff>
<country xml:lang="fr">États-Unis</country>
<wicri:regionArea># see nlm:aff country strict</wicri:regionArea>
</affiliation>
<affiliation wicri:level="1">
<nlm:aff id="AF7">
<institution>State Key Laboratory of Respiratory Disease, Guangzhou Institute of Respiratory Health, The First Affiliated Hospital of Guangzhou Medical University</institution>
, Guangzhou,
<country>People’s Republic of China</country>
</nlm:aff>
<country xml:lang="fr">République populaire de Chine</country>
<wicri:regionArea># see nlm:aff country strict</wicri:regionArea>
</affiliation>
</author>
<author>
<name sortKey="Zhang, Linqi" sort="Zhang, Linqi" uniqKey="Zhang L" first="Linqi" last="Zhang">Linqi Zhang</name>
<affiliation wicri:level="1">
<nlm:aff id="AF1">
<institution>Comprehensive AIDS Research Center, Collaborative Innovation Center for Diagnosis and Treatment of Infectious Diseases, Beijing Advanced Innovation Center for Structural Biology, Department of Basic Medical Sciences, School of Medicine, Tsinghua University</institution>
, Beijing,
<country>People’s Republic of China</country>
</nlm:aff>
<country xml:lang="fr">République populaire de Chine</country>
<wicri:regionArea># see nlm:aff country strict</wicri:regionArea>
</affiliation>
</author>
</analytic>
<series>
<title level="j">Emerging Microbes & Infections</title>
<idno type="eISSN">2222-1751</idno>
<imprint>
<date when="2019">2019</date>
</imprint>
</series>
</biblStruct>
</sourceDesc>
</fileDesc>
<profileDesc>
<textClass>
<keywords scheme="KwdEn" xml:lang="en">
<term>Adenoviridae (genetics)</term>
<term>Administration, Intranasal</term>
<term>Animals</term>
<term>Animals, Genetically Modified</term>
<term>Antibodies, Neutralizing (blood)</term>
<term>Antibodies, Viral (blood)</term>
<term>Coronavirus Infections (prevention & control)</term>
<term>Drug Carriers (administration & dosage)</term>
<term>Humans</term>
<term>Immunization, Passive</term>
<term>Mice, Inbred BALB C</term>
<term>Middle East Respiratory Syndrome Coronavirus (genetics)</term>
<term>Middle East Respiratory Syndrome Coronavirus (immunology)</term>
<term>Spike Glycoprotein, Coronavirus (genetics)</term>
<term>Spike Glycoprotein, Coronavirus (immunology)</term>
<term>Survival Analysis</term>
<term>T-Lymphocytes (immunology)</term>
<term>Treatment Outcome</term>
<term>Vaccines, Synthetic (administration & dosage)</term>
<term>Vaccines, Synthetic (genetics)</term>
<term>Vaccines, Synthetic (immunology)</term>
<term>Viral Vaccines (administration & dosage)</term>
<term>Viral Vaccines (genetics)</term>
<term>Viral Vaccines (immunology)</term>
</keywords>
<keywords scheme="KwdFr" xml:lang="fr">
<term>Adenoviridae (génétique)</term>
<term>Administration par voie nasale</term>
<term>Analyse de survie</term>
<term>Animal génétiquement modifié</term>
<term>Animaux</term>
<term>Anticorps antiviraux (sang)</term>
<term>Anticorps neutralisants (sang)</term>
<term>Coronavirus du syndrome respiratoire du Moyen-Orient (génétique)</term>
<term>Coronavirus du syndrome respiratoire du Moyen-Orient (immunologie)</term>
<term>Glycoprotéine de spicule des coronavirus (génétique)</term>
<term>Glycoprotéine de spicule des coronavirus (immunologie)</term>
<term>Humains</term>
<term>Immunisation passive</term>
<term>Infections à coronavirus ()</term>
<term>Lymphocytes T (immunologie)</term>
<term>Résultat thérapeutique</term>
<term>Souris de lignée BALB C</term>
<term>Vaccins antiviraux (administration et posologie)</term>
<term>Vaccins antiviraux (génétique)</term>
<term>Vaccins antiviraux (immunologie)</term>
<term>Vaccins synthétiques (administration et posologie)</term>
<term>Vaccins synthétiques (génétique)</term>
<term>Vaccins synthétiques (immunologie)</term>
<term>Vecteurs de médicaments (administration et posologie)</term>
</keywords>
<keywords scheme="MESH" type="chemical" qualifier="administration & dosage" xml:lang="en">
<term>Drug Carriers</term>
<term>Vaccines, Synthetic</term>
<term>Viral Vaccines</term>
</keywords>
<keywords scheme="MESH" type="chemical" qualifier="blood" xml:lang="en">
<term>Antibodies, Neutralizing</term>
<term>Antibodies, Viral</term>
</keywords>
<keywords scheme="MESH" qualifier="administration et posologie" xml:lang="fr">
<term>Vaccins antiviraux</term>
<term>Vaccins synthétiques</term>
<term>Vecteurs de médicaments</term>
</keywords>
<keywords scheme="MESH" qualifier="genetics" xml:lang="en">
<term>Adenoviridae</term>
<term>Middle East Respiratory Syndrome Coronavirus</term>
<term>Spike Glycoprotein, Coronavirus</term>
<term>Vaccines, Synthetic</term>
<term>Viral Vaccines</term>
</keywords>
<keywords scheme="MESH" qualifier="génétique" xml:lang="fr">
<term>Adenoviridae</term>
<term>Coronavirus du syndrome respiratoire du Moyen-Orient</term>
<term>Glycoprotéine de spicule des coronavirus</term>
<term>Vaccins antiviraux</term>
<term>Vaccins synthétiques</term>
</keywords>
<keywords scheme="MESH" qualifier="immunologie" xml:lang="fr">
<term>Coronavirus du syndrome respiratoire du Moyen-Orient</term>
<term>Glycoprotéine de spicule des coronavirus</term>
<term>Lymphocytes T</term>
<term>Vaccins antiviraux</term>
<term>Vaccins synthétiques</term>
</keywords>
<keywords scheme="MESH" qualifier="immunology" xml:lang="en">
<term>Middle East Respiratory Syndrome Coronavirus</term>
<term>Spike Glycoprotein, Coronavirus</term>
<term>T-Lymphocytes</term>
<term>Vaccines, Synthetic</term>
<term>Viral Vaccines</term>
</keywords>
<keywords scheme="MESH" qualifier="prevention & control" xml:lang="en">
<term>Coronavirus Infections</term>
</keywords>
<keywords scheme="MESH" qualifier="sang" xml:lang="fr">
<term>Anticorps antiviraux</term>
<term>Anticorps neutralisants</term>
</keywords>
<keywords scheme="MESH" xml:lang="en">
<term>Administration, Intranasal</term>
<term>Animals</term>
<term>Animals, Genetically Modified</term>
<term>Humans</term>
<term>Immunization, Passive</term>
<term>Mice, Inbred BALB C</term>
<term>Survival Analysis</term>
<term>Treatment Outcome</term>
</keywords>
<keywords scheme="MESH" xml:lang="fr">
<term>Administration par voie nasale</term>
<term>Analyse de survie</term>
<term>Animal génétiquement modifié</term>
<term>Animaux</term>
<term>Humains</term>
<term>Immunisation passive</term>
<term>Infections à coronavirus</term>
<term>Résultat thérapeutique</term>
<term>Souris de lignée BALB C</term>
</keywords>
</textClass>
</profileDesc>
</teiHeader>
<front>
<div type="abstract" xml:lang="en">
<title>ABSTRACT</title>
<p>The recently identified Middle East Respiratory Syndrome Coronavirus (MERS-CoV) causes severe and fatal acute respiratory illness in humans. However, no approved prophylactic and therapeutic interventions are currently available. The MERS-CoV envelope spike protein serves as a crucial target for neutralizing antibodies and vaccine development, as it plays a critical role in mediating viral entry through interactions with the cellular receptor, dipeptidyl peptidase 4 (DPP4). Here, we constructed a recombinant rare serotype of the chimpanzee adenovirus 68 (AdC68) that expresses full-length MERS-CoV S protein (AdC68-S). Single intranasal immunization with AdC68-S induced robust and sustained neutralizing antibody and T cell responses in BALB/c mice. In a human DPP4 knock-in (hDPP4-KI) mouse model, it completely protected against lethal challenge with a mouse-adapted MERS-CoV (MERS-CoV-MA). Passive transfer of immune sera to naïve hDPP4-KI mice also provided survival advantages from lethal MERS-CoV-MA challenge. Analysis of sera absorption and isolated monoclonal antibodies from immunized mice demonstrated that the potent and broad neutralizing activity was largely attributed to antibodies targeting the receptor binding domain (RBD) of the S protein. These results show that AdC68-S can induce protective immune responses in mice and represent a promising candidate for further development against MERS-CoV infection in both dromedaries and humans.</p>
</div>
</front>
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<country>
<li>République populaire de Chine</li>
<li>États-Unis</li>
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<name sortKey="Shan, Sisi" sort="Shan, Sisi" uniqKey="Shan S" first="Sisi" last="Shan">Sisi Shan</name>
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<name sortKey="Zhang, Chao" sort="Zhang, Chao" uniqKey="Zhang C" first="Chao" last="Zhang">Chao Zhang</name>
<name sortKey="Zhang, Chao" sort="Zhang, Chao" uniqKey="Zhang C" first="Chao" last="Zhang">Chao Zhang</name>
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<name sortKey="Zhou, Dongming" sort="Zhou, Dongming" uniqKey="Zhou D" first="Dongming" last="Zhou">Dongming Zhou</name>
<name sortKey="Zhou, Haixia" sort="Zhou, Haixia" uniqKey="Zhou H" first="Haixia" last="Zhou">Haixia Zhou</name>
<name sortKey="Zhou, Panpan" sort="Zhou, Panpan" uniqKey="Zhou P" first="Panpan" last="Zhou">Panpan Zhou</name>
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