Receptor-binding domain of MERS-CoV with optimal immunogen dosage and immunization interval protects human transgenic mice from MERS-CoV infection.
Identifieur interne : 000C17 ( Main/Merge ); précédent : 000C16; suivant : 000C18Receptor-binding domain of MERS-CoV with optimal immunogen dosage and immunization interval protects human transgenic mice from MERS-CoV infection.
Auteurs : Yufei Wang [République populaire de Chine] ; Wanbo Tai [États-Unis] ; Jie Yang [États-Unis] ; Guangyu Zhao [République populaire de Chine] ; Shihui Sun [République populaire de Chine] ; Chien-Te K. Tseng [États-Unis] ; Shibo Jiang [États-Unis] ; Yusen Zhou [République populaire de Chine] ; Lanying Du [États-Unis] ; Jimin Gao [République populaire de Chine]Source :
- Human vaccines & immunotherapeutics [ 2164-554X ] ; 2017.
Descripteurs français
- KwdFr :
- Animaux, Calendrier vaccinal, Coronavirus du syndrome respiratoire du Moyen-Orient (immunologie), Domaines protéiques (immunologie), Femelle, Glycoprotéine de spicule des coronavirus (immunologie), Humains, Infections à coronavirus (), Mâle, Souris SCID, Souris de lignée BALB C, Souris transgéniques, Vaccins antiviraux (administration et posologie), Vaccins antiviraux (immunologie), Vaccins synthétiques (administration et posologie), Vaccins synthétiques (immunologie).
- MESH :
- administration et posologie : Vaccins antiviraux, Vaccins synthétiques.
- immunologie : Coronavirus du syndrome respiratoire du Moyen-Orient, Domaines protéiques, Glycoprotéine de spicule des coronavirus, Vaccins antiviraux, Vaccins synthétiques.
- Animaux, Calendrier vaccinal, Femelle, Humains, Infections à coronavirus, Mâle, Souris SCID, Souris de lignée BALB C, Souris transgéniques.
English descriptors
- KwdEn :
- Animals, Coronavirus Infections (prevention & control), Female, Humans, Immunization Schedule, Male, Mice, Inbred BALB C, Mice, SCID, Mice, Transgenic, Middle East Respiratory Syndrome Coronavirus (immunology), Protein Domains (immunology), Spike Glycoprotein, Coronavirus (immunology), Vaccines, Synthetic (administration & dosage), Vaccines, Synthetic (immunology), Viral Vaccines (administration & dosage), Viral Vaccines (immunology).
- MESH :
- chemical , administration & dosage : Vaccines, Synthetic, Viral Vaccines.
- chemical , immunology : Spike Glycoprotein, Coronavirus, Vaccines, Synthetic, Viral Vaccines.
- immunology : Middle East Respiratory Syndrome Coronavirus, Protein Domains.
- prevention & control : Coronavirus Infections.
- Animals, Female, Humans, Immunization Schedule, Male, Mice, Inbred BALB C, Mice, SCID, Mice, Transgenic.
Abstract
Middle East respiratory syndrome (MERS) continues to raise worldwide concerns due to its pandemic potential. Increased MERS cases and no licensed MERS vaccines highlight the need to develop safe and effective vaccines against MERS. We have previously demonstrated that a receptor-binding domain (RBD) fragment containing residues 377-588 of MERS-coronavirus (MERS-CoV) spike protein is a critical neutralizing domain and an important vaccine target. Nevertheless, its optimal immunogen dosage and immunization interval, key factors for human-used vaccines that induce protective immunity, have never been investigated. In this study, we optimized these criteria using a recombinant MERS-CoV RBD protein fused with Fc (S377-588-Fc) and utilized the optimal immunization schedule to evaluate the protective efficacy of RBD against MERS-CoV infection in human dipeptidyl peptidase 4 transgenic (hDPP4-Tg) mice. Compared with one dose and 2 doses at 1-, 2-, and 3-week intervals, a regimen of 2 doses of this protein separated by an interval of 4 weeks induced the strongest antibody response and neutralizing antibodies against MERS-CoV infection, and maintained at a high level during the detection period. Notably, RBD protein at the optimal dosage and interval protected hDPP4-Tg mice against lethal MERS-CoV challenge, and the protection was positively correlated with serum neutralizing antibodies. Taken together, the optimal immunogen dosage and immunization interval identified in this study will provide useful guidelines for further development of MERS-CoV RBD-based vaccines for human use.
DOI: 10.1080/21645515.2017.1296994
PubMed: 28277821
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Kimball Research Institute , New York Blood Center , New York , NY , USA.</nlm:affiliation><country xml:lang="fr">États-Unis</country><wicri:regionArea>b Lindsley F. Kimball Research Institute , New York Blood Center , New York , NY </wicri:regionArea><placeName><region type="state">État de New York</region></placeName></affiliation></author><author><name sortKey="Yang, Jie" sort="Yang, Jie" uniqKey="Yang J" first="Jie" last="Yang">Jie Yang</name><affiliation wicri:level="2"><nlm:affiliation>b Lindsley F. Kimball Research Institute , New York Blood Center , New York , NY , USA.</nlm:affiliation><country xml:lang="fr">États-Unis</country><wicri:regionArea>b Lindsley F. 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Tseng</name><affiliation wicri:level="2"><nlm:affiliation>d Department of Microbiology and Immunology and Center for Biodefense and Emerging Disease , University of Texas Medical Branch , Galveston , TX , USA.</nlm:affiliation><country xml:lang="fr">États-Unis</country><wicri:regionArea>d Department of Microbiology and Immunology and Center for Biodefense and Emerging Disease , University of Texas Medical Branch , Galveston , TX </wicri:regionArea><placeName><region type="state">Texas</region></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:affiliation>b Lindsley F. Kimball Research Institute , New York Blood Center , New York , NY , USA.</nlm:affiliation><country xml:lang="fr">États-Unis</country><wicri:regionArea>b Lindsley F. Kimball Research Institute , New York Blood Center , New York , NY </wicri:regionArea><placeName><region type="state">État de New York</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="1"><nlm:affiliation>a School of Medical Laboratory Science , Wenzhou Medical University , Wenzhou , Zhejiang , China.</nlm:affiliation><country xml:lang="fr">République populaire de Chine</country><wicri:regionArea>a School of Medical Laboratory Science , Wenzhou Medical University , Wenzhou , Zhejiang </wicri:regionArea><wicri:noRegion>Zhejiang </wicri:noRegion></affiliation></author><author><name sortKey="Du, Lanying" sort="Du, Lanying" uniqKey="Du L" first="Lanying" last="Du">Lanying Du</name><affiliation wicri:level="2"><nlm:affiliation>b Lindsley F. Kimball Research Institute , New York Blood Center , New York , NY , USA.</nlm:affiliation><country xml:lang="fr">États-Unis</country><wicri:regionArea>b Lindsley F. Kimball Research Institute , New York Blood Center , New York , NY </wicri:regionArea><placeName><region type="state">État de New York</region></placeName></affiliation></author><author><name sortKey="Gao, Jimin" sort="Gao, Jimin" uniqKey="Gao J" first="Jimin" last="Gao">Jimin Gao</name><affiliation wicri:level="1"><nlm:affiliation>a School of Medical Laboratory Science , Wenzhou Medical University , Wenzhou , Zhejiang , China.</nlm:affiliation><country xml:lang="fr">République populaire de Chine</country><wicri:regionArea>a School of Medical Laboratory Science , Wenzhou Medical University , Wenzhou , Zhejiang </wicri:regionArea><wicri:noRegion>Zhejiang </wicri:noRegion></affiliation></author></analytic><series><title level="j">Human vaccines & immunotherapeutics</title><idno type="eISSN">2164-554X</idno><imprint><date when="2017" type="published">2017</date></imprint></series></biblStruct></sourceDesc></fileDesc><profileDesc><textClass><keywords scheme="KwdEn" xml:lang="en"><term>Animals</term><term>Coronavirus Infections (prevention & control)</term><term>Female</term><term>Humans</term><term>Immunization Schedule</term><term>Male</term><term>Mice, Inbred BALB C</term><term>Mice, SCID</term><term>Mice, Transgenic</term><term>Middle East Respiratory Syndrome Coronavirus (immunology)</term><term>Protein Domains (immunology)</term><term>Spike Glycoprotein, Coronavirus (immunology)</term><term>Vaccines, Synthetic (administration & dosage)</term><term>Vaccines, Synthetic (immunology)</term><term>Viral Vaccines (administration & dosage)</term><term>Viral Vaccines (immunology)</term></keywords><keywords scheme="KwdFr" xml:lang="fr"><term>Animaux</term><term>Calendrier vaccinal</term><term>Coronavirus du syndrome respiratoire du Moyen-Orient (immunologie)</term><term>Domaines protéiques (immunologie)</term><term>Femelle</term><term>Glycoprotéine de spicule des coronavirus (immunologie)</term><term>Humains</term><term>Infections à coronavirus ()</term><term>Mâle</term><term>Souris SCID</term><term>Souris de lignée BALB C</term><term>Souris transgéniques</term><term>Vaccins antiviraux (administration et posologie)</term><term>Vaccins antiviraux (immunologie)</term><term>Vaccins synthétiques (administration et posologie)</term><term>Vaccins synthétiques (immunologie)</term></keywords><keywords scheme="MESH" type="chemical" qualifier="administration & dosage" xml:lang="en"><term>Vaccines, Synthetic</term><term>Viral Vaccines</term></keywords><keywords scheme="MESH" type="chemical" qualifier="immunology" xml:lang="en"><term>Spike Glycoprotein, Coronavirus</term><term>Vaccines, Synthetic</term><term>Viral Vaccines</term></keywords><keywords scheme="MESH" qualifier="administration et posologie" xml:lang="fr"><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>Domaines protéiques</term><term>Glycoprotéine de spicule des coronavirus</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>Protein Domains</term></keywords><keywords scheme="MESH" qualifier="prevention & control" xml:lang="en"><term>Coronavirus Infections</term></keywords><keywords scheme="MESH" xml:lang="en"><term>Animals</term><term>Female</term><term>Humans</term><term>Immunization Schedule</term><term>Male</term><term>Mice, Inbred BALB C</term><term>Mice, SCID</term><term>Mice, Transgenic</term></keywords><keywords scheme="MESH" xml:lang="fr"><term>Animaux</term><term>Calendrier vaccinal</term><term>Femelle</term><term>Humains</term><term>Infections à coronavirus</term><term>Mâle</term><term>Souris SCID</term><term>Souris de lignée BALB C</term><term>Souris transgéniques</term></keywords></textClass></profileDesc></teiHeader><front><div type="abstract" xml:lang="en">Middle East respiratory syndrome (MERS) continues to raise worldwide concerns due to its pandemic potential. Increased MERS cases and no licensed MERS vaccines highlight the need to develop safe and effective vaccines against MERS. We have previously demonstrated that a receptor-binding domain (RBD) fragment containing residues 377-588 of MERS-coronavirus (MERS-CoV) spike protein is a critical neutralizing domain and an important vaccine target. Nevertheless, its optimal immunogen dosage and immunization interval, key factors for human-used vaccines that induce protective immunity, have never been investigated. In this study, we optimized these criteria using a recombinant MERS-CoV RBD protein fused with Fc (S377-588-Fc) and utilized the optimal immunization schedule to evaluate the protective efficacy of RBD against MERS-CoV infection in human dipeptidyl peptidase 4 transgenic (hDPP4-Tg) mice. Compared with one dose and 2 doses at 1-, 2-, and 3-week intervals, a regimen of 2 doses of this protein separated by an interval of 4 weeks induced the strongest antibody response and neutralizing antibodies against MERS-CoV infection, and maintained at a high level during the detection period. Notably, RBD protein at the optimal dosage and interval protected hDPP4-Tg mice against lethal MERS-CoV challenge, and the protection was positively correlated with serum neutralizing antibodies. Taken together, the optimal immunogen dosage and immunization interval identified in this study will provide useful guidelines for further development of MERS-CoV RBD-based vaccines for human use.</div></front></TEI></record>Pour manipuler ce document sous Unix (Dilib)
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