Optimization of antigen dose for a receptor-binding domain-based subunit vaccine against MERS coronavirus
Identifieur interne : 001641 ( Main/Exploration ); précédent : 001640; suivant : 001642Optimization of antigen dose for a receptor-binding domain-based subunit vaccine against MERS coronavirus
Auteurs : Jian Tang [République populaire de Chine, États-Unis] ; Naru Zhang [États-Unis] ; Xinrong Tao [États-Unis] ; Guangyu Zhao [République populaire de Chine] ; Yan Guo [République populaire de Chine] ; Chien-Te K. Tseng [États-Unis] ; Shibo Jiang [États-Unis, République populaire de Chine] ; Lanying Du [États-Unis] ; Yusen Zhou [République populaire de Chine]Source :
- Human Vaccines & Immunotherapeutics [ 2164-5515 ] ; 2015.
Descripteurs français
- KwdFr :
- Adjuvants immunologiques (administration et posologie), Animaux, Anticorps antiviraux (sang), Anticorps neutralisants (sang), Antigènes viraux (administration et posologie), Antigènes viraux (génétique), Antigènes viraux (immunologie), Coronavirus du syndrome respiratoire du Moyen-Orient (immunologie), Femelle, Fragments Fc des immunoglobulines (administration et posologie), Fragments Fc des immunoglobulines (génétique), Fragments Fc des immunoglobulines (immunologie), Humains, Immunité cellulaire, Immunité humorale, Infections à coronavirus (), Polysorbates (administration et posologie), Protéines de fusion recombinantes (administration et posologie), Protéines de fusion recombinantes (génétique), Protéines de fusion recombinantes (immunologie), Souris de lignée BALB C, Squalène (administration et posologie), Vaccins antiviraux (administration et posologie), Vaccins antiviraux (génétique), Vaccins antiviraux (immunologie), Vaccins sous-unitaires (administration et posologie), Vaccins sous-unitaires (génétique), Vaccins sous-unitaires (immunologie).
- MESH :
- administration et posologie : Adjuvants immunologiques, Antigènes viraux, Fragments Fc des immunoglobulines, Polysorbates, Protéines de fusion recombinantes, Squalène, Vaccins antiviraux, Vaccins sous-unitaires.
- génétique : Antigènes viraux, Fragments Fc des immunoglobulines, Protéines de fusion recombinantes, Vaccins antiviraux, Vaccins sous-unitaires.
- immunologie : Antigènes viraux, Coronavirus du syndrome respiratoire du Moyen-Orient, Fragments Fc des immunoglobulines, Protéines de fusion recombinantes, Vaccins antiviraux, Vaccins sous-unitaires.
- sang : Anticorps antiviraux, Anticorps neutralisants.
- Animaux, Femelle, Humains, Immunité cellulaire, Immunité humorale, Infections à coronavirus, Souris de lignée BALB C.
English descriptors
- KwdEn :
- Adjuvants, Immunologic (administration & dosage), Animals, Antibodies, Neutralizing (blood), Antibodies, Viral (blood), Antigens, Viral (administration & dosage), Antigens, Viral (genetics), Antigens, Viral (immunology), Coronavirus Infections (prevention & control), Female, Humans, Immunity, Cellular, Immunity, Humoral, Immunoglobulin Fc Fragments (administration & dosage), Immunoglobulin Fc Fragments (genetics), Immunoglobulin Fc Fragments (immunology), Mice, Inbred BALB C, Middle East Respiratory Syndrome Coronavirus (immunology), Polysorbates (administration & dosage), Recombinant Fusion Proteins (administration & dosage), Recombinant Fusion Proteins (genetics), Recombinant Fusion Proteins (immunology), Squalene (administration & dosage), Vaccines, Subunit (administration & dosage), Vaccines, Subunit (genetics), Vaccines, Subunit (immunology), Viral Vaccines (administration & dosage), Viral Vaccines (genetics), Viral Vaccines (immunology).
- MESH :
- chemical , administration & dosage : Adjuvants, Immunologic, Antigens, Viral, Immunoglobulin Fc Fragments, Polysorbates, Recombinant Fusion Proteins, Squalene, Vaccines, Subunit, Viral Vaccines.
- chemical , blood : Antibodies, Neutralizing, Antibodies, Viral.
- chemical , genetics : Antigens, Viral, Immunoglobulin Fc Fragments, Recombinant Fusion Proteins, Vaccines, Subunit, Viral Vaccines.
- chemical , immunology : Antigens, Viral, Immunoglobulin Fc Fragments, Recombinant Fusion Proteins, Vaccines, Subunit, Viral Vaccines.
- immunology : Middle East Respiratory Syndrome Coronavirus.
- prevention & control : Coronavirus Infections.
- Animals, Female, Humans, Immunity, Cellular, Immunity, Humoral, Mice, Inbred BALB C.
Abstract
Middle East respiratory syndrome (MERS) is an emerging infectious disease caused by MERS coronavirus (MERS-CoV). The continuous increase of MERS cases has posed a serious threat to public health worldwide, calling for development of safe and effective MERS vaccines. We have previously shown that a recombinant protein containing residues 377–588 of MERS-CoV receptor-binding domain (RBD) fused with human Fc (S377-588-Fc) induced highly potent anti-MERS-CoV neutralizing antibodies in the presence of MF59 adjuvant. Here we optimized the doses of S377-588-Fc using MF59 as an adjuvant in order to elicit strong immune responses with minimal amount of antigen. Our results showed that S377-588-Fc at 1 μg was able to induce in the immunized mice potent humoral and cellular immune responses. Particularly, S377-588-Fc at 1 μg elicited strong neutralizing antibody responses against both pseudotyped and live MERS-CoV similar to those induced at 5 and 20 μg, respectively. These results suggest that this RBD-based subunit MERS vaccine candidate at the dose as low as one μg is sufficiently potent to induce strong humoral and cellular immune responses, including neutralizing antibodies, against MERS-CoV infection, thus providing guidance for determining the optimal dosage of RBD-based MERS vaccines in the future clinical trials and for applying the dose-sparing strategy in other subunit vaccine trials.
Url:
DOI: 10.1080/21645515.2015.1021527
PubMed: 25874632
PubMed Central: 4514392
Affiliations:
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Le document en format XML
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Central South University;</institution>, Changsha,<country>China</country></nlm:aff><country xml:lang="fr">République populaire de Chine</country><wicri:regionArea># see nlm:aff country strict</wicri:regionArea></affiliation><affiliation wicri:level="1"><nlm:aff id="af0002"><institution>State Key Laboratory of Pathogen and Biosecurity; Beijing Institute of Microbiology and Epidemiology;</institution>, Beijing,<country>China</country></nlm:aff><country xml:lang="fr">République populaire de Chine</country><wicri:regionArea># see nlm:aff country strict</wicri:regionArea></affiliation><affiliation wicri:level="1"><nlm:aff id="af0003"><institution>Lindsley F Kimball Research Institute; New York Blood Center;</institution>, New York, NY,<country>USA</country></nlm:aff><country xml:lang="fr">États-Unis</country><wicri:regionArea># see nlm:aff country strict</wicri:regionArea></affiliation></author><author><name sortKey="Zhang, Naru" sort="Zhang, Naru" uniqKey="Zhang N" first="Naru" last="Zhang">Naru Zhang</name><affiliation wicri:level="1"><nlm:aff id="af0003"><institution>Lindsley F Kimball Research Institute; New York Blood Center;</institution>, New York, NY,<country>USA</country></nlm:aff><country xml:lang="fr">États-Unis</country><wicri:regionArea># see nlm:aff country strict</wicri:regionArea></affiliation></author><author><name sortKey="Tao, Xinrong" sort="Tao, Xinrong" uniqKey="Tao X" first="Xinrong" last="Tao">Xinrong Tao</name><affiliation wicri:level="1"><nlm:aff id="af0004"><institution>Department of Microbiology and Immunology and Center for Biodefense and Emerging Disease; University of Texas Medical Branch;</institution>, Galveston, TX,<country>USA</country></nlm:aff><country xml:lang="fr">États-Unis</country><wicri:regionArea># see nlm:aff country strict</wicri:regionArea></affiliation></author><author><name sortKey="Zhao, Guangyu" sort="Zhao, Guangyu" uniqKey="Zhao G" first="Guangyu" last="Zhao">Guangyu Zhao</name><affiliation wicri:level="1"><nlm:aff id="af0002"><institution>State Key Laboratory of Pathogen and Biosecurity; Beijing Institute of Microbiology and Epidemiology;</institution>, Beijing,<country>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="Guo, Yan" sort="Guo, Yan" uniqKey="Guo Y" first="Yan" last="Guo">Yan Guo</name><affiliation wicri:level="1"><nlm:aff id="af0002"><institution>State Key Laboratory of Pathogen and Biosecurity; Beijing Institute of Microbiology and Epidemiology;</institution>, Beijing,<country>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="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="1"><nlm:aff id="af0004"><institution>Department of Microbiology and Immunology and Center for Biodefense and Emerging Disease; University of Texas Medical Branch;</institution>, Galveston, TX,<country>USA</country></nlm:aff><country xml:lang="fr">États-Unis</country><wicri:regionArea># see nlm:aff country strict</wicri:regionArea></affiliation></author><author><name sortKey="Jiang, Shibo" sort="Jiang, Shibo" uniqKey="Jiang S" first="Shibo" last="Jiang">Shibo Jiang</name><affiliation wicri:level="1"><nlm:aff id="af0003"><institution>Lindsley F Kimball Research Institute; New York Blood Center;</institution>, New York, NY,<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="af0005"><institution>Key Laboratory of Medical Molecular Virology of Ministries of Education and Health; Shanghai Medical College and Institute of Medical Microbiology; Fudan University;</institution>, Shanghai,<country>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="Du, Lanying" sort="Du, Lanying" uniqKey="Du L" first="Lanying" last="Du">Lanying Du</name><affiliation wicri:level="1"><nlm:aff id="af0003"><institution>Lindsley F Kimball Research Institute; New York Blood Center;</institution>, New York, NY,<country>USA</country></nlm:aff><country xml:lang="fr">États-Unis</country><wicri:regionArea># see nlm:aff country strict</wicri:regionArea></affiliation></author><author><name sortKey="Zhou, Yusen" sort="Zhou, Yusen" uniqKey="Zhou Y" first="Yusen" last="Zhou">Yusen Zhou</name><affiliation wicri:level="1"><nlm:aff id="af0001"><institution>Xiang-Ya Medical College; Central South University;</institution>, Changsha,<country>China</country></nlm:aff><country xml:lang="fr">République populaire de Chine</country><wicri:regionArea># see nlm:aff country strict</wicri:regionArea></affiliation><affiliation wicri:level="1"><nlm:aff id="af0002"><institution>State Key Laboratory of Pathogen and Biosecurity; Beijing Institute of Microbiology and Epidemiology;</institution>, Beijing,<country>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">Human Vaccines & Immunotherapeutics</title><idno type="ISSN">2164-5515</idno><idno type="eISSN">2164-554X</idno><imprint><date when="2015">2015</date></imprint></series></biblStruct></sourceDesc></fileDesc><profileDesc><textClass><keywords scheme="KwdEn" xml:lang="en"><term>Adjuvants, Immunologic (administration & dosage)</term><term>Animals</term><term>Antibodies, Neutralizing (blood)</term><term>Antibodies, Viral (blood)</term><term>Antigens, Viral (administration & dosage)</term><term>Antigens, Viral (genetics)</term><term>Antigens, Viral (immunology)</term><term>Coronavirus Infections (prevention & control)</term><term>Female</term><term>Humans</term><term>Immunity, Cellular</term><term>Immunity, Humoral</term><term>Immunoglobulin Fc Fragments (administration & dosage)</term><term>Immunoglobulin Fc Fragments (genetics)</term><term>Immunoglobulin Fc Fragments (immunology)</term><term>Mice, Inbred BALB C</term><term>Middle East Respiratory Syndrome Coronavirus (immunology)</term><term>Polysorbates (administration & dosage)</term><term>Recombinant Fusion Proteins (administration & dosage)</term><term>Recombinant Fusion Proteins (genetics)</term><term>Recombinant Fusion Proteins (immunology)</term><term>Squalene (administration & dosage)</term><term>Vaccines, Subunit (administration & dosage)</term><term>Vaccines, Subunit (genetics)</term><term>Vaccines, Subunit (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>Adjuvants immunologiques (administration et posologie)</term><term>Animaux</term><term>Anticorps antiviraux (sang)</term><term>Anticorps neutralisants (sang)</term><term>Antigènes viraux (administration et posologie)</term><term>Antigènes viraux (génétique)</term><term>Antigènes viraux (immunologie)</term><term>Coronavirus du syndrome respiratoire du Moyen-Orient (immunologie)</term><term>Femelle</term><term>Fragments Fc des immunoglobulines (administration et posologie)</term><term>Fragments Fc des immunoglobulines (génétique)</term><term>Fragments Fc des immunoglobulines (immunologie)</term><term>Humains</term><term>Immunité cellulaire</term><term>Immunité humorale</term><term>Infections à coronavirus ()</term><term>Polysorbates (administration et posologie)</term><term>Protéines de fusion recombinantes (administration et posologie)</term><term>Protéines de fusion recombinantes (génétique)</term><term>Protéines de fusion recombinantes (immunologie)</term><term>Souris de lignée BALB C</term><term>Squalène (administration et posologie)</term><term>Vaccins antiviraux (administration et posologie)</term><term>Vaccins antiviraux (génétique)</term><term>Vaccins antiviraux (immunologie)</term><term>Vaccins sous-unitaires (administration et posologie)</term><term>Vaccins sous-unitaires (génétique)</term><term>Vaccins sous-unitaires (immunologie)</term></keywords><keywords scheme="MESH" type="chemical" qualifier="administration & dosage" xml:lang="en"><term>Adjuvants, Immunologic</term><term>Antigens, Viral</term><term>Immunoglobulin Fc Fragments</term><term>Polysorbates</term><term>Recombinant Fusion Proteins</term><term>Squalene</term><term>Vaccines, Subunit</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" type="chemical" qualifier="genetics" xml:lang="en"><term>Antigens, Viral</term><term>Immunoglobulin Fc Fragments</term><term>Recombinant Fusion Proteins</term><term>Vaccines, Subunit</term><term>Viral Vaccines</term></keywords><keywords scheme="MESH" type="chemical" qualifier="immunology" xml:lang="en"><term>Antigens, Viral</term><term>Immunoglobulin Fc Fragments</term><term>Recombinant Fusion Proteins</term><term>Vaccines, Subunit</term><term>Viral Vaccines</term></keywords><keywords scheme="MESH" qualifier="administration et posologie" xml:lang="fr"><term>Adjuvants immunologiques</term><term>Antigènes viraux</term><term>Fragments Fc des immunoglobulines</term><term>Polysorbates</term><term>Protéines de fusion recombinantes</term><term>Squalène</term><term>Vaccins antiviraux</term><term>Vaccins sous-unitaires</term></keywords><keywords scheme="MESH" qualifier="génétique" xml:lang="fr"><term>Antigènes viraux</term><term>Fragments Fc des immunoglobulines</term><term>Protéines de fusion recombinantes</term><term>Vaccins antiviraux</term><term>Vaccins sous-unitaires</term></keywords><keywords scheme="MESH" qualifier="immunologie" xml:lang="fr"><term>Antigènes viraux</term><term>Coronavirus du syndrome respiratoire du Moyen-Orient</term><term>Fragments Fc des immunoglobulines</term><term>Protéines de fusion recombinantes</term><term>Vaccins antiviraux</term><term>Vaccins sous-unitaires</term></keywords><keywords scheme="MESH" qualifier="immunology" xml:lang="en"><term>Middle East Respiratory Syndrome Coronavirus</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>Animals</term><term>Female</term><term>Humans</term><term>Immunity, Cellular</term><term>Immunity, Humoral</term><term>Mice, Inbred BALB C</term></keywords><keywords scheme="MESH" xml:lang="fr"><term>Animaux</term><term>Femelle</term><term>Humains</term><term>Immunité cellulaire</term><term>Immunité humorale</term><term>Infections à coronavirus</term><term>Souris de lignée BALB C</term></keywords></textClass></profileDesc></teiHeader><front><div type="abstract" xml:lang="en"><p>Middle East respiratory syndrome (MERS) is an emerging infectious disease caused by MERS coronavirus (MERS-CoV). The continuous increase of MERS cases has posed a serious threat to public health worldwide, calling for development of safe and effective MERS vaccines. We have previously shown that a recombinant protein containing residues 377–588 of MERS-CoV receptor-binding domain (RBD) fused with human Fc (S377-588-Fc) induced highly potent anti-MERS-CoV neutralizing antibodies in the presence of MF59 adjuvant. Here we optimized the doses of S377-588-Fc using MF59 as an adjuvant in order to elicit strong immune responses with minimal amount of antigen. Our results showed that S377-588-Fc at 1 μg was able to induce in the immunized mice potent humoral and cellular immune responses. Particularly, S377-588-Fc at 1 μg elicited strong neutralizing antibody responses against both pseudotyped and live MERS-CoV similar to those induced at 5 and 20 μg, respectively. These results suggest that this RBD-based subunit MERS vaccine candidate at the dose as low as one μg is sufficiently potent to induce strong humoral and cellular immune responses, including neutralizing antibodies, against MERS-CoV infection, thus providing guidance for determining the optimal dosage of RBD-based MERS vaccines in the future clinical trials and for applying the dose-sparing strategy in other subunit vaccine trials.</p></div></front><back><div1 type="bibliography"><listBibl><biblStruct><analytic><author><name sortKey="Drosten, C" uniqKey="Drosten C">C Drosten</name></author><author><name sortKey="Seilmaier, M" uniqKey="Seilmaier M">M Seilmaier</name></author><author><name sortKey="Corman, Vm" uniqKey="Corman V">VM Corman</name></author><author><name sortKey="Hartmann, W" uniqKey="Hartmann W">W Hartmann</name></author><author><name sortKey="Scheible, G" uniqKey="Scheible G">G Scheible</name></author><author><name sortKey="Sack, S" uniqKey="Sack S">S 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Tseng</name><name sortKey="Zhang, Naru" sort="Zhang, Naru" uniqKey="Zhang N" first="Naru" last="Zhang">Naru Zhang</name></country></tree></affiliations></record>Pour manipuler ce document sous Unix (Dilib)
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