A Truncated Receptor-Binding Domain of MERS-CoV Spike Protein Potently Inhibits MERS-CoV Infection and Induces Strong Neutralizing Antibody Responses: Implication for Developing Therapeutics and Vaccines
Identifieur interne : 002071 ( Main/Exploration ); précédent : 002070; suivant : 002072A Truncated Receptor-Binding Domain of MERS-CoV Spike Protein Potently Inhibits MERS-CoV Infection and Induces Strong Neutralizing Antibody Responses: Implication for Developing Therapeutics and Vaccines
Auteurs : Lanying Du [États-Unis] ; Zhihua Kou [République populaire de Chine] ; Cuiqing Ma [États-Unis] ; Xinrong Tao [États-Unis] ; Lili Wang [États-Unis] ; Guangyu Zhao [République populaire de Chine] ; Yaoqing Chen [États-Unis] ; Fei Yu [États-Unis] ; Chien-Te K. Tseng [États-Unis] ; Yusen Zhou [République populaire de Chine] ; Shibo Jiang [États-Unis, République populaire de Chine]Source :
- PLoS ONE [ 1932-6203 ] ; 2013.
Descripteurs français
- KwdFr :
- Animaux, Anticorps neutralisants (immunologie), Coronavirus (physiologie), Cristallographie aux rayons X, Femelle, Glycoprotéine de spicule des coronavirus (métabolisme), Humains, Immunoglobuline G (métabolisme), Infections de l'appareil respiratoire (immunologie), Infections de l'appareil respiratoire (traitement médicamenteux), Infections de l'appareil respiratoire (virologie), Production d'anticorps (immunologie), Protéines recombinantes (immunologie), Récepteur Fc (métabolisme), Souris, Souris de lignée BALB C, Spécificité des anticorps (immunologie), Structure tertiaire des protéines, Sérums immuns (immunologie), Vaccination, Vaccins (immunologie), Vaccins antiviraux (immunologie), Vaccins antiviraux (usage thérapeutique).
- MESH :
- immunologie : Anticorps neutralisants, Infections de l'appareil respiratoire, Production d'anticorps, Protéines recombinantes, Spécificité des anticorps, Sérums immuns, Vaccins, Vaccins antiviraux.
- métabolisme : Glycoprotéine de spicule des coronavirus, Immunoglobuline G, Récepteur Fc.
- physiologie : Coronavirus.
- traitement médicamenteux : Infections de l'appareil respiratoire.
- usage thérapeutique : Vaccins antiviraux.
- virologie : Infections de l'appareil respiratoire.
- Animaux, Cristallographie aux rayons X, Femelle, Humains, Souris, Souris de lignée BALB C, Structure tertiaire des protéines, Vaccination.
English descriptors
- KwdEn :
- Animals, Antibodies, Neutralizing (immunology), Antibody Formation (immunology), Antibody Specificity (immunology), Coronavirus (physiology), Crystallography, X-Ray, Female, Humans, Immune Sera (immunology), Immunoglobulin G (metabolism), Mice, Mice, Inbred BALB C, Protein Structure, Tertiary, Receptors, Fc (metabolism), Recombinant Proteins (immunology), Respiratory Tract Infections (drug therapy), Respiratory Tract Infections (immunology), Respiratory Tract Infections (virology), Spike Glycoprotein, Coronavirus (metabolism), Vaccination, Vaccines (immunology), Viral Vaccines (immunology), Viral Vaccines (therapeutic use).
- MESH :
- chemical , immunology : Antibodies, Neutralizing, Immune Sera, Recombinant Proteins, Vaccines, Viral Vaccines.
- drug therapy : Respiratory Tract Infections.
- immunology : Antibody Formation, Antibody Specificity, Respiratory Tract Infections.
- chemical , metabolism : Immunoglobulin G, Receptors, Fc, Spike Glycoprotein, Coronavirus.
- physiology : Coronavirus.
- chemical , therapeutic use : Viral Vaccines.
- virology : Respiratory Tract Infections.
- Animals, Crystallography, X-Ray, Female, Humans, Mice, Mice, Inbred BALB C, Protein Structure, Tertiary, Vaccination.
Abstract
An emerging respiratory infectious disease with high mortality, Middle East respiratory syndrome (MERS), is caused by a novel coronavirus (MERS-CoV). It was first reported in 2012 in Saudi Arabia and has now spread to eight countries. Development of effective therapeutics and vaccines is crucial to save lives and halt the spread of MERS-CoV. Here, we show that a recombinant protein containing a 212-amino acid fragment (residues 377-588) in the truncated receptor-binding domain (RBD: residues 367–606) of MERS-CoV spike (S) protein fused with human IgG Fc fragment (S377-588-Fc) is highly expressed in the culture supernatant of transfected 293T cells. The purified S377-588-Fc protein efficiently binds to dipeptidyl peptidase 4 (DPP4), the receptor of MERS-CoV, and potently inhibited MERS-CoV infection, suggesting its potential to be further developed as a therapeutic modality for treating MERS-CoV infection and saving the patients’ lives. The recombinant S377-588-Fc is able to induce in the vaccinated mice strong MERS-CoV S-specific antibodies, which blocks the binding of RBD to DPP4 receptor and effectively neutralizes MERS-CoV infection. These findings indicate that this truncated RBD protein shows promise for further development as an effective and safe vaccine for the prevention of MERS-CoV infection.
Url:
DOI: 10.1371/journal.pone.0081587
PubMed: 24324708
PubMed Central: 3852489
Affiliations:
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Kimball Research Institute, New York Blood Center, New York, New York, United States of America</addr-line></nlm:aff><country xml:lang="fr">États-Unis</country><wicri:regionArea>Lindsley F. Kimball Research Institute, New York Blood Center, New York, New York</wicri:regionArea><placeName><region type="state">État de New York</region></placeName></affiliation></author><author><name sortKey="Kou, Zhihua" sort="Kou, Zhihua" uniqKey="Kou Z" first="Zhihua" last="Kou">Zhihua Kou</name><affiliation wicri:level="3"><nlm:aff id="aff2"><addr-line>State Key Laboratory of Pathogen and Biosecurity, Beijing Institute of Microbiology and Epidemiology, Beijing, China</addr-line></nlm:aff><country xml:lang="fr">République populaire de Chine</country><wicri:regionArea>State Key Laboratory of Pathogen and Biosecurity, Beijing Institute of Microbiology and Epidemiology, Beijing</wicri:regionArea><placeName><settlement type="city">Pékin</settlement></placeName></affiliation></author><author><name sortKey="Ma, Cuiqing" sort="Ma, Cuiqing" uniqKey="Ma C" first="Cuiqing" last="Ma">Cuiqing Ma</name><affiliation wicri:level="2"><nlm:aff id="aff1"><addr-line>Lindsley F. Kimball Research Institute, New York Blood Center, New York, New York, United States of America</addr-line></nlm:aff><country xml:lang="fr">États-Unis</country><wicri:regionArea>Lindsley F. Kimball Research Institute, New York Blood Center, New York, New York</wicri:regionArea><placeName><region type="state">État de New York</region></placeName></affiliation></author><author><name sortKey="Tao, Xinrong" sort="Tao, Xinrong" uniqKey="Tao X" first="Xinrong" last="Tao">Xinrong Tao</name><affiliation wicri:level="2"><nlm:aff id="aff3"><addr-line>Departments of Microbiology and Immunology, University of Texas Medical Branch, Galveston, Texas, United States of America</addr-line></nlm:aff><country xml:lang="fr">États-Unis</country><wicri:regionArea>Departments of Microbiology and Immunology, University of Texas Medical Branch, Galveston, Texas</wicri:regionArea><placeName><region type="state">Texas</region></placeName></affiliation></author><author><name sortKey="Wang, Lili" sort="Wang, Lili" uniqKey="Wang L" first="Lili" last="Wang">Lili Wang</name><affiliation wicri:level="2"><nlm:aff id="aff1"><addr-line>Lindsley F. Kimball Research Institute, New York Blood Center, New York, New York, United States of America</addr-line></nlm:aff><country xml:lang="fr">États-Unis</country><wicri:regionArea>Lindsley F. Kimball Research Institute, New York Blood Center, New York, New York</wicri:regionArea><placeName><region type="state">État de New York</region></placeName></affiliation></author><author><name sortKey="Zhao, Guangyu" sort="Zhao, Guangyu" uniqKey="Zhao G" first="Guangyu" last="Zhao">Guangyu Zhao</name><affiliation wicri:level="3"><nlm:aff id="aff2"><addr-line>State Key Laboratory of Pathogen and Biosecurity, Beijing Institute of Microbiology and Epidemiology, Beijing, China</addr-line></nlm:aff><country xml:lang="fr">République populaire de Chine</country><wicri:regionArea>State Key Laboratory of Pathogen and Biosecurity, Beijing Institute of Microbiology and Epidemiology, Beijing</wicri:regionArea><placeName><settlement type="city">Pékin</settlement></placeName></affiliation></author><author><name sortKey="Chen, Yaoqing" sort="Chen, Yaoqing" uniqKey="Chen Y" first="Yaoqing" last="Chen">Yaoqing Chen</name><affiliation wicri:level="2"><nlm:aff id="aff4"><addr-line>Department of Pharmacology, University of Minnesota Medical School, Minneapolis, Minnesota, United States of America</addr-line></nlm:aff><country xml:lang="fr">États-Unis</country><wicri:regionArea>Department of Pharmacology, University of Minnesota Medical School, Minneapolis, Minnesota</wicri:regionArea><placeName><region type="state">Minnesota</region></placeName></affiliation></author><author><name sortKey="Yu, Fei" sort="Yu, Fei" uniqKey="Yu F" first="Fei" last="Yu">Fei Yu</name><affiliation wicri:level="2"><nlm:aff id="aff1"><addr-line>Lindsley F. Kimball Research Institute, New York Blood Center, New York, New York, United States of America</addr-line></nlm:aff><country xml:lang="fr">États-Unis</country><wicri:regionArea>Lindsley F. Kimball Research Institute, New York Blood Center, New York, New York</wicri:regionArea><placeName><region type="state">État de New York</region></placeName></affiliation></author><author><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><affiliation wicri:level="2"><nlm:aff id="aff3"><addr-line>Departments of Microbiology and Immunology, University of Texas Medical Branch, Galveston, Texas, United States of America</addr-line></nlm:aff><country xml:lang="fr">États-Unis</country><wicri:regionArea>Departments of Microbiology and Immunology, University of Texas Medical Branch, Galveston, Texas</wicri:regionArea><placeName><region type="state">Texas</region></placeName></affiliation></author><author><name sortKey="Zhou, Yusen" sort="Zhou, Yusen" uniqKey="Zhou Y" first="Yusen" last="Zhou">Yusen Zhou</name><affiliation wicri:level="3"><nlm:aff id="aff2"><addr-line>State Key Laboratory of Pathogen and Biosecurity, Beijing Institute of Microbiology and Epidemiology, Beijing, China</addr-line></nlm:aff><country xml:lang="fr">République populaire de Chine</country><wicri:regionArea>State Key Laboratory of Pathogen and Biosecurity, Beijing Institute of Microbiology and Epidemiology, Beijing</wicri:regionArea><placeName><settlement type="city">Pékin</settlement></placeName></affiliation></author><author><name sortKey="Jiang, Shibo" sort="Jiang, Shibo" uniqKey="Jiang S" first="Shibo" last="Jiang">Shibo Jiang</name><affiliation wicri:level="2"><nlm:aff id="aff1"><addr-line>Lindsley F. Kimball Research Institute, New York Blood Center, New York, New York, United States of America</addr-line></nlm:aff><country xml:lang="fr">États-Unis</country><wicri:regionArea>Lindsley F. Kimball Research Institute, New York Blood Center, New York, New York</wicri:regionArea><placeName><region type="state">État de New York</region></placeName></affiliation><affiliation wicri:level="1"><nlm:aff id="aff5"><addr-line>Key Laboratory of Medical Molecular Virology of Ministries of Education and Health, Shanghai Medical College and Institute of Medical Microbi, Fudan University, Shanghai, China</addr-line></nlm:aff><country xml:lang="fr">République populaire de Chine</country><wicri:regionArea>Key Laboratory of Medical Molecular Virology of Ministries of Education and Health, Shanghai Medical College and Institute of Medical Microbi, Fudan University, Shanghai</wicri:regionArea><wicri:noRegion>Shanghai</wicri:noRegion></affiliation></author></analytic><series><title level="j">PLoS ONE</title><idno type="eISSN">1932-6203</idno><imprint><date when="2013">2013</date></imprint></series></biblStruct></sourceDesc></fileDesc><profileDesc><textClass><keywords scheme="KwdEn" xml:lang="en"><term>Animals</term><term>Antibodies, Neutralizing (immunology)</term><term>Antibody Formation (immunology)</term><term>Antibody Specificity (immunology)</term><term>Coronavirus (physiology)</term><term>Crystallography, X-Ray</term><term>Female</term><term>Humans</term><term>Immune Sera (immunology)</term><term>Immunoglobulin G (metabolism)</term><term>Mice</term><term>Mice, Inbred BALB C</term><term>Protein Structure, Tertiary</term><term>Receptors, Fc (metabolism)</term><term>Recombinant Proteins (immunology)</term><term>Respiratory Tract Infections (drug therapy)</term><term>Respiratory Tract Infections (immunology)</term><term>Respiratory Tract Infections (virology)</term><term>Spike Glycoprotein, Coronavirus (metabolism)</term><term>Vaccination</term><term>Vaccines (immunology)</term><term>Viral Vaccines (immunology)</term><term>Viral Vaccines (therapeutic use)</term></keywords><keywords scheme="KwdFr" xml:lang="fr"><term>Animaux</term><term>Anticorps neutralisants (immunologie)</term><term>Coronavirus (physiologie)</term><term>Cristallographie aux rayons X</term><term>Femelle</term><term>Glycoprotéine de spicule des coronavirus (métabolisme)</term><term>Humains</term><term>Immunoglobuline G (métabolisme)</term><term>Infections de l'appareil respiratoire (immunologie)</term><term>Infections de l'appareil respiratoire (traitement médicamenteux)</term><term>Infections de l'appareil respiratoire (virologie)</term><term>Production d'anticorps (immunologie)</term><term>Protéines recombinantes (immunologie)</term><term>Récepteur Fc (métabolisme)</term><term>Souris</term><term>Souris de lignée BALB C</term><term>Spécificité des anticorps (immunologie)</term><term>Structure tertiaire des protéines</term><term>Sérums immuns (immunologie)</term><term>Vaccination</term><term>Vaccins (immunologie)</term><term>Vaccins antiviraux (immunologie)</term><term>Vaccins antiviraux (usage thérapeutique)</term></keywords><keywords scheme="MESH" type="chemical" qualifier="immunology" xml:lang="en"><term>Antibodies, Neutralizing</term><term>Immune Sera</term><term>Recombinant Proteins</term><term>Vaccines</term><term>Viral Vaccines</term></keywords><keywords scheme="MESH" qualifier="drug therapy" xml:lang="en"><term>Respiratory Tract Infections</term></keywords><keywords scheme="MESH" qualifier="immunologie" xml:lang="fr"><term>Anticorps neutralisants</term><term>Infections de l'appareil respiratoire</term><term>Production d'anticorps</term><term>Protéines recombinantes</term><term>Spécificité des anticorps</term><term>Sérums immuns</term><term>Vaccins</term><term>Vaccins antiviraux</term></keywords><keywords scheme="MESH" qualifier="immunology" xml:lang="en"><term>Antibody Formation</term><term>Antibody Specificity</term><term>Respiratory Tract Infections</term></keywords><keywords scheme="MESH" type="chemical" qualifier="metabolism" xml:lang="en"><term>Immunoglobulin G</term><term>Receptors, Fc</term><term>Spike Glycoprotein, Coronavirus</term></keywords><keywords scheme="MESH" qualifier="métabolisme" xml:lang="fr"><term>Glycoprotéine de spicule des coronavirus</term><term>Immunoglobuline G</term><term>Récepteur Fc</term></keywords><keywords scheme="MESH" qualifier="physiologie" xml:lang="fr"><term>Coronavirus</term></keywords><keywords scheme="MESH" qualifier="physiology" xml:lang="en"><term>Coronavirus</term></keywords><keywords scheme="MESH" type="chemical" qualifier="therapeutic use" xml:lang="en"><term>Viral Vaccines</term></keywords><keywords scheme="MESH" qualifier="traitement médicamenteux" xml:lang="fr"><term>Infections de l'appareil respiratoire</term></keywords><keywords scheme="MESH" qualifier="usage thérapeutique" xml:lang="fr"><term>Vaccins antiviraux</term></keywords><keywords scheme="MESH" qualifier="virologie" xml:lang="fr"><term>Infections de l'appareil respiratoire</term></keywords><keywords scheme="MESH" qualifier="virology" xml:lang="en"><term>Respiratory Tract Infections</term></keywords><keywords scheme="MESH" xml:lang="en"><term>Animals</term><term>Crystallography, X-Ray</term><term>Female</term><term>Humans</term><term>Mice</term><term>Mice, Inbred BALB C</term><term>Protein Structure, Tertiary</term><term>Vaccination</term></keywords><keywords scheme="MESH" xml:lang="fr"><term>Animaux</term><term>Cristallographie aux rayons X</term><term>Femelle</term><term>Humains</term><term>Souris</term><term>Souris de lignée BALB C</term><term>Structure tertiaire des protéines</term><term>Vaccination</term></keywords></textClass></profileDesc></teiHeader><front><div type="abstract" xml:lang="en"><p>An emerging respiratory infectious disease with high mortality, Middle East respiratory syndrome (MERS), is caused by a novel coronavirus (MERS-CoV). It was first reported in 2012 in Saudi Arabia and has now spread to eight countries. Development of effective therapeutics and vaccines is crucial to save lives and halt the spread of MERS-CoV. Here, we show that a recombinant protein containing a 212-amino acid fragment (residues 377-588) in the truncated receptor-binding domain (RBD: residues 367–606) of MERS-CoV spike (S) protein fused with human IgG Fc fragment (S377-588-Fc) is highly expressed in the culture supernatant of transfected 293T cells. The purified S377-588-Fc protein efficiently binds to dipeptidyl peptidase 4 (DPP4), the receptor of MERS-CoV, and potently inhibited MERS-CoV infection, suggesting its potential to be further developed as a therapeutic modality for treating MERS-CoV infection and saving the patients’ lives. The recombinant S377-588-Fc is able to induce in the vaccinated mice strong MERS-CoV S-specific antibodies, which blocks the binding of RBD to DPP4 receptor and effectively neutralizes MERS-CoV infection. These findings indicate that this truncated RBD protein shows promise for further development as an effective and safe vaccine for the prevention of MERS-CoV infection.</p></div></front><back><div1 type="bibliography"><listBibl><biblStruct><analytic><author><name sortKey="Zaki, Am" uniqKey="Zaki A">AM Zaki</name></author><author><name sortKey="Van Boheemen, S" uniqKey="Van Boheemen S">S van Boheemen</name></author><author><name sortKey="Bestebroer, Tm" uniqKey="Bestebroer T">TM Bestebroer</name></author><author><name sortKey="Osterhaus, Adme" uniqKey="Osterhaus A">ADME Osterhaus</name></author><author><name sortKey="Fouchier, Ram" uniqKey="Fouchier R">RAM Fouchier</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Memish, Za" uniqKey="Memish Z">ZA Memish</name></author><author><name sortKey="Zumla, Ai" uniqKey="Zumla A">AI Zumla</name></author><author><name sortKey="Al Hakeem, Rf" uniqKey="Al Hakeem R">RF Al-Hakeem</name></author><author><name 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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="Wang, Lili" sort="Wang, Lili" uniqKey="Wang L" first="Lili" last="Wang">Lili Wang</name><name sortKey="Yu, Fei" sort="Yu, Fei" uniqKey="Yu F" first="Fei" last="Yu">Fei Yu</name></country><country name="République populaire de Chine"><noRegion><name sortKey="Kou, Zhihua" sort="Kou, Zhihua" uniqKey="Kou Z" first="Zhihua" last="Kou">Zhihua Kou</name></noRegion><name sortKey="Jiang, Shibo" sort="Jiang, Shibo" uniqKey="Jiang S" first="Shibo" last="Jiang">Shibo Jiang</name><name sortKey="Zhao, Guangyu" sort="Zhao, Guangyu" uniqKey="Zhao G" first="Guangyu" last="Zhao">Guangyu Zhao</name><name sortKey="Zhou, Yusen" sort="Zhou, Yusen" uniqKey="Zhou Y" first="Yusen" last="Zhou">Yusen Zhou</name></country></tree></affiliations></record>Pour manipuler ce document sous Unix (Dilib)
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