Immunogenicity of Candidate MERS-CoV DNA Vaccines Based on the Spike Protein
Identifieur interne : 000D45 ( Main/Exploration ); précédent : 000D44; suivant : 000D46Immunogenicity of Candidate MERS-CoV DNA Vaccines Based on the Spike Protein
Auteurs : Sawsan S. Al-Amri [Arabie saoudite] ; Ayman T. Abbas [Arabie saoudite, Égypte] ; Loai A. Siddiq [Arabie saoudite] ; Abrar Alghamdi [Arabie saoudite] ; Mohammad A. Sanki [Arabie saoudite] ; Muhanna K. Al-Muhanna [Arabie saoudite] ; Rowa Y. Alhabbab [Arabie saoudite] ; Esam I. Azhar [Arabie saoudite] ; Xuguang Li [Canada] ; Anwar M. Hashem [Arabie saoudite]Source :
- Scientific Reports [ 2045-2322 ] ; 2017.
Descripteurs français
- KwdFr :
- Animaux, Anticorps antiviraux (immunologie), Anticorps neutralisants (immunologie), Cellules Vero, Chameaux, Coronavirus du syndrome respiratoire du Moyen-Orient (génétique), Coronavirus du syndrome respiratoire du Moyen-Orient (immunologie), Coronavirus du syndrome respiratoire du Moyen-Orient (isolement et purification), Femelle, Glycoprotéine de spicule des coronavirus (génétique), Glycoprotéine de spicule des coronavirus (immunologie), Humains, Immunisation, Immunoglobuline G (immunologie), Immunogénicité des vaccins, Infections à coronavirus (), Infections à coronavirus (immunologie), Modèles animaux de maladie humaine, Souris, Tests de neutralisation, Vaccins antiviraux (génétique), Vaccins antiviraux (immunologie), Vaccins à ADN (génétique), Vaccins à ADN (immunologie).
- MESH :
- génétique : Coronavirus du syndrome respiratoire du Moyen-Orient, Glycoprotéine de spicule des coronavirus, Vaccins antiviraux, Vaccins à ADN.
- immunologie : Anticorps antiviraux, Anticorps neutralisants, Coronavirus du syndrome respiratoire du Moyen-Orient, Glycoprotéine de spicule des coronavirus, Immunoglobuline G, Infections à coronavirus, Vaccins antiviraux, Vaccins à ADN.
- isolement et purification : Coronavirus du syndrome respiratoire du Moyen-Orient.
- Animaux, Cellules Vero, Chameaux, Femelle, Humains, Immunisation, Immunogénicité des vaccins, Infections à coronavirus, Modèles animaux de maladie humaine, Souris, Tests de neutralisation.
English descriptors
- KwdEn :
- Animals, Antibodies, Neutralizing (immunology), Antibodies, Viral (immunology), Camelus, Chlorocebus aethiops, Coronavirus Infections (immunology), Coronavirus Infections (prevention & control), Disease Models, Animal, Female, Humans, Immunization, Immunogenicity, Vaccine, Immunoglobulin G (immunology), Mice, Middle East Respiratory Syndrome Coronavirus (genetics), Middle East Respiratory Syndrome Coronavirus (immunology), Middle East Respiratory Syndrome Coronavirus (isolation & purification), Neutralization Tests, Spike Glycoprotein, Coronavirus (genetics), Spike Glycoprotein, Coronavirus (immunology), Vaccines, DNA (genetics), Vaccines, DNA (immunology), Vero Cells, Viral Vaccines (genetics), Viral Vaccines (immunology).
- MESH :
- chemical , genetics : Spike Glycoprotein, Coronavirus, Vaccines, DNA, Viral Vaccines.
- chemical , immunology : Antibodies, Neutralizing, Antibodies, Viral, Immunoglobulin G, Spike Glycoprotein, Coronavirus, Vaccines, DNA, Viral Vaccines.
- genetics : Middle East Respiratory Syndrome Coronavirus.
- immunology : Coronavirus Infections, Middle East Respiratory Syndrome Coronavirus.
- isolation & purification : Middle East Respiratory Syndrome Coronavirus.
- prevention & control : Coronavirus Infections.
- Animals, Camelus, Chlorocebus aethiops, Disease Models, Animal, Female, Humans, Immunization, Immunogenicity, Vaccine, Mice, Neutralization Tests, Vero Cells.
Abstract
MERS-coronavirus is a novel zoonotic pathogen which spread rapidly to >25 countries since 2012. Its apparent endemicity and the wide spread of its reservoir host (dromedary camels) in the Arabian Peninsula highlight the ongoing public health threat of this virus. Therefore, development of effective prophylactic vaccine needs to be urgently explored given that there are no approved prophylactics or therapeutics for humans or animals to date. Different vaccine candidates have been investigated but serious safety concerns remain over protein or full-length spike (S) protein-based vaccines. Here, we investigated the immunogenicity of naked DNA vaccines expressing different fragments of MERS-CoV S protein in mice. We found that plasmids expressing full-length (pS) or S1-subunit (pS1) could induce significant levels of S1-specific antibodies (Abs) but with distinct IgG isotype patterns. Specifically, pS1 immunization elicited a balanced Th1/Th2 response and generally higher levels of all IgG isotypes compared to pS vaccination. Interestingly, only mice immunized with pS1 demonstrated significant S1-specific cellular immune response. Importantly, both constructs induced cross-neutralizing Abs against multiple strains of human and camel origins. These results indicate that vaccines expressing S1-subunit of the MERS-CoV S protein could represent a potential vaccine candidate without the possible safety concerns associated with full-length protein-based vaccines.
The online version of this article (doi:10.1038/srep44875) contains supplementary material, which is available to authorized users.
Url:
DOI: 10.1038/srep44875
PubMed: 28332568
PubMed Central: 5362948
Affiliations:
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Le document en format XML
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Sanki</name><affiliation wicri:level="1"><nlm:aff id="Aff3"><institution-wrap><institution-id institution-id-type="GRID">grid.412126.2</institution-id><institution-id institution-id-type="ISNI">0000 0004 0607 9688</institution-id><institution>Hematology Laboratory, King Abdulaziz University Hospital,</institution></institution-wrap>Jeddah, Saudi Arabia</nlm:aff><country xml:lang="fr">Arabie saoudite</country><wicri:regionArea>Jeddah</wicri:regionArea></affiliation></author><author><name sortKey="Al Muhanna, Muhanna K" sort="Al Muhanna, Muhanna K" uniqKey="Al Muhanna M" first="Muhanna K." last="Al-Muhanna">Muhanna K. Al-Muhanna</name><affiliation wicri:level="1"><nlm:aff id="Aff4"><institution-wrap><institution-id institution-id-type="GRID">grid.452562.2</institution-id><institution-id institution-id-type="ISNI">0000 0000 8808 6435</institution-id><institution>Materials Science Research Institute, National Nanotechnology Center, King Abdulaziz City for Science and Technology (KACST),</institution></institution-wrap>Riyadh, Saudi Arabia</nlm:aff><country xml:lang="fr">Arabie saoudite</country><wicri:regionArea>Riyadh</wicri:regionArea></affiliation></author><author><name sortKey="Alhabbab, Rowa Y" sort="Alhabbab, Rowa Y" uniqKey="Alhabbab R" first="Rowa Y." last="Alhabbab">Rowa Y. Alhabbab</name><affiliation wicri:level="1"><nlm:aff id="Aff1"><institution-wrap><institution-id institution-id-type="GRID">grid.412125.1</institution-id><institution-id institution-id-type="ISNI">0000 0001 0619 1117</institution-id><institution>Special Infectious Agents Unit, King Fahd Medical Research Center, King Abdulaziz University,</institution></institution-wrap>Jeddah, Saudi Arabia</nlm:aff><country xml:lang="fr">Arabie saoudite</country><wicri:regionArea>Jeddah</wicri:regionArea></affiliation><affiliation wicri:level="1"><nlm:aff id="Aff5"><institution-wrap><institution-id institution-id-type="GRID">grid.412125.1</institution-id><institution-id institution-id-type="ISNI">0000 0001 0619 1117</institution-id><institution>Department of Medical Laboratory Technology,</institution><institution>Faculty of Applied Medical Sciences, King Abdulaziz University,</institution></institution-wrap>Jeddah, Saudi Arabia</nlm:aff><country xml:lang="fr">Arabie saoudite</country><wicri:regionArea>Jeddah</wicri:regionArea></affiliation></author><author><name sortKey="Azhar, Esam I" sort="Azhar, Esam I" uniqKey="Azhar E" first="Esam I." last="Azhar">Esam I. Azhar</name><affiliation wicri:level="1"><nlm:aff id="Aff1"><institution-wrap><institution-id institution-id-type="GRID">grid.412125.1</institution-id><institution-id institution-id-type="ISNI">0000 0001 0619 1117</institution-id><institution>Special Infectious Agents Unit, King Fahd Medical Research Center, King Abdulaziz University,</institution></institution-wrap>Jeddah, Saudi Arabia</nlm:aff><country xml:lang="fr">Arabie saoudite</country><wicri:regionArea>Jeddah</wicri:regionArea></affiliation><affiliation wicri:level="1"><nlm:aff id="Aff5"><institution-wrap><institution-id institution-id-type="GRID">grid.412125.1</institution-id><institution-id institution-id-type="ISNI">0000 0001 0619 1117</institution-id><institution>Department of Medical Laboratory Technology,</institution><institution>Faculty of Applied Medical Sciences, King Abdulaziz University,</institution></institution-wrap>Jeddah, Saudi Arabia</nlm:aff><country xml:lang="fr">Arabie saoudite</country><wicri:regionArea>Jeddah</wicri:regionArea></affiliation></author><author><name sortKey="Li, Xuguang" sort="Li, Xuguang" uniqKey="Li X" first="Xuguang" last="Li">Xuguang Li</name><affiliation><nlm:aff id="Aff6">Center for Vaccine Evaluation, ,</nlm:aff></affiliation><affiliation wicri:level="1"><nlm:aff id="Aff8">Biologics and Genetic Therapies Directorate, Ontario, Canada</nlm:aff><country xml:lang="fr">Canada</country><wicri:regionArea>Biologics and Genetic Therapies Directorate, Ontario</wicri:regionArea><wicri:noRegion>Ontario</wicri:noRegion></affiliation><affiliation><nlm:aff id="Aff9">Health Canada; Ottawa, ,</nlm:aff></affiliation></author><author><name sortKey="Hashem, Anwar M" sort="Hashem, Anwar M" uniqKey="Hashem A" first="Anwar M." last="Hashem">Anwar M. Hashem</name><affiliation wicri:level="1"><nlm:aff id="Aff1"><institution-wrap><institution-id institution-id-type="GRID">grid.412125.1</institution-id><institution-id institution-id-type="ISNI">0000 0001 0619 1117</institution-id><institution>Special Infectious Agents Unit, King Fahd Medical Research Center, King Abdulaziz University,</institution></institution-wrap>Jeddah, Saudi Arabia</nlm:aff><country xml:lang="fr">Arabie saoudite</country><wicri:regionArea>Jeddah</wicri:regionArea></affiliation><affiliation wicri:level="1"><nlm:aff id="Aff7"><institution-wrap><institution-id institution-id-type="GRID">grid.412125.1</institution-id><institution-id institution-id-type="ISNI">0000 0001 0619 1117</institution-id><institution>Department of Medical Microbiology and Parasitology,</institution><institution>Faculty of Medicine, King Abdulaziz University,</institution></institution-wrap>Jeddah, Saudi Arabia</nlm:aff><country xml:lang="fr">Arabie saoudite</country><wicri:regionArea>Jeddah</wicri:regionArea></affiliation></author></analytic><series><title level="j">Scientific Reports</title><idno type="eISSN">2045-2322</idno><imprint><date when="2017">2017</date></imprint></series></biblStruct></sourceDesc></fileDesc><profileDesc><textClass><keywords scheme="KwdEn" xml:lang="en"><term>Animals</term><term>Antibodies, Neutralizing (immunology)</term><term>Antibodies, Viral (immunology)</term><term>Camelus</term><term>Chlorocebus aethiops</term><term>Coronavirus Infections (immunology)</term><term>Coronavirus Infections (prevention & control)</term><term>Disease Models, Animal</term><term>Female</term><term>Humans</term><term>Immunization</term><term>Immunogenicity, Vaccine</term><term>Immunoglobulin G (immunology)</term><term>Mice</term><term>Middle East Respiratory Syndrome Coronavirus (genetics)</term><term>Middle East Respiratory Syndrome Coronavirus (immunology)</term><term>Middle East Respiratory Syndrome Coronavirus (isolation & purification)</term><term>Neutralization Tests</term><term>Spike Glycoprotein, Coronavirus (genetics)</term><term>Spike Glycoprotein, Coronavirus (immunology)</term><term>Vaccines, DNA (genetics)</term><term>Vaccines, DNA (immunology)</term><term>Vero Cells</term><term>Viral Vaccines (genetics)</term><term>Viral Vaccines (immunology)</term></keywords><keywords scheme="KwdFr" xml:lang="fr"><term>Animaux</term><term>Anticorps antiviraux (immunologie)</term><term>Anticorps neutralisants (immunologie)</term><term>Cellules Vero</term><term>Chameaux</term><term>Coronavirus du syndrome respiratoire du Moyen-Orient (génétique)</term><term>Coronavirus du syndrome respiratoire du Moyen-Orient (immunologie)</term><term>Coronavirus du syndrome respiratoire du Moyen-Orient (isolement et purification)</term><term>Femelle</term><term>Glycoprotéine de spicule des coronavirus (génétique)</term><term>Glycoprotéine de spicule des coronavirus (immunologie)</term><term>Humains</term><term>Immunisation</term><term>Immunoglobuline G (immunologie)</term><term>Immunogénicité des vaccins</term><term>Infections à coronavirus ()</term><term>Infections à coronavirus (immunologie)</term><term>Modèles animaux de maladie humaine</term><term>Souris</term><term>Tests de neutralisation</term><term>Vaccins antiviraux (génétique)</term><term>Vaccins antiviraux (immunologie)</term><term>Vaccins à ADN (génétique)</term><term>Vaccins à ADN (immunologie)</term></keywords><keywords scheme="MESH" type="chemical" qualifier="genetics" xml:lang="en"><term>Spike Glycoprotein, Coronavirus</term><term>Vaccines, DNA</term><term>Viral Vaccines</term></keywords><keywords scheme="MESH" type="chemical" qualifier="immunology" xml:lang="en"><term>Antibodies, Neutralizing</term><term>Antibodies, Viral</term><term>Immunoglobulin G</term><term>Spike Glycoprotein, Coronavirus</term><term>Vaccines, DNA</term><term>Viral Vaccines</term></keywords><keywords scheme="MESH" qualifier="genetics" xml:lang="en"><term>Middle East Respiratory Syndrome Coronavirus</term></keywords><keywords scheme="MESH" qualifier="génétique" xml:lang="fr"><term>Coronavirus du syndrome respiratoire du Moyen-Orient</term><term>Glycoprotéine de spicule des coronavirus</term><term>Vaccins antiviraux</term><term>Vaccins à ADN</term></keywords><keywords scheme="MESH" qualifier="immunologie" xml:lang="fr"><term>Anticorps antiviraux</term><term>Anticorps neutralisants</term><term>Coronavirus du syndrome respiratoire du Moyen-Orient</term><term>Glycoprotéine de spicule des coronavirus</term><term>Immunoglobuline G</term><term>Infections à coronavirus</term><term>Vaccins antiviraux</term><term>Vaccins à ADN</term></keywords><keywords scheme="MESH" qualifier="immunology" xml:lang="en"><term>Coronavirus Infections</term><term>Middle East Respiratory Syndrome Coronavirus</term></keywords><keywords scheme="MESH" qualifier="isolation & purification" xml:lang="en"><term>Middle East Respiratory Syndrome Coronavirus</term></keywords><keywords scheme="MESH" qualifier="isolement et purification" xml:lang="fr"><term>Coronavirus du syndrome respiratoire du Moyen-Orient</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>Camelus</term><term>Chlorocebus aethiops</term><term>Disease Models, Animal</term><term>Female</term><term>Humans</term><term>Immunization</term><term>Immunogenicity, Vaccine</term><term>Mice</term><term>Neutralization Tests</term><term>Vero Cells</term></keywords><keywords scheme="MESH" xml:lang="fr"><term>Animaux</term><term>Cellules Vero</term><term>Chameaux</term><term>Femelle</term><term>Humains</term><term>Immunisation</term><term>Immunogénicité des vaccins</term><term>Infections à coronavirus</term><term>Modèles animaux de maladie humaine</term><term>Souris</term><term>Tests de neutralisation</term></keywords></textClass></profileDesc></teiHeader><front><div type="abstract" xml:lang="en"><p id="Par1">MERS-coronavirus is a novel zoonotic pathogen which spread rapidly to >25 countries since 2012. Its apparent endemicity and the wide spread of its reservoir host (dromedary camels) in the Arabian Peninsula highlight the ongoing public health threat of this virus. Therefore, development of effective prophylactic vaccine needs to be urgently explored given that there are no approved prophylactics or therapeutics for humans or animals to date. Different vaccine candidates have been investigated but serious safety concerns remain over protein or full-length spike (S) protein-based vaccines. Here, we investigated the immunogenicity of naked DNA vaccines expressing different fragments of MERS-CoV S protein in mice. We found that plasmids expressing full-length (pS) or S1-subunit (pS1) could induce significant levels of S1-specific antibodies (Abs) but with distinct IgG isotype patterns. Specifically, pS1 immunization elicited a balanced Th1/Th2 response and generally higher levels of all IgG isotypes compared to pS vaccination. Interestingly, only mice immunized with pS1 demonstrated significant S1-specific cellular immune response. Importantly, both constructs induced cross-neutralizing Abs against multiple strains of human and camel origins. These results indicate that vaccines expressing S1-subunit of the MERS-CoV S protein could represent a potential vaccine candidate without the possible safety concerns associated with full-length protein-based vaccines.</p><sec><title>Supplementary information</title><p>The online version of this article (doi:10.1038/srep44875) contains supplementary material, which is available to authorized users.</p></sec></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, Ad" uniqKey="Osterhaus A">AD Osterhaus</name></author><author><name sortKey="Fouchier, Ra" uniqKey="Fouchier R">RA Fouchier</name></author></analytic></biblStruct><biblStruct><analytic><author><name 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Jiang</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Du, L" uniqKey="Du L">L Du</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Tang, Xc" uniqKey="Tang X">XC Tang</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Corti, D" uniqKey="Corti D">D Corti</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Pascal, Ke" uniqKey="Pascal K">KE Pascal</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Agrawal, As" uniqKey="Agrawal A">AS Agrawal</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Lu, G" uniqKey="Lu G">G Lu</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Wang, L" uniqKey="Wang L">L Wang</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Muthumani, K" uniqKey="Muthumani K">K 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saoudite</li><li>Canada</li><li>Égypte</li></country></list><tree><country name="Arabie saoudite"><noRegion><name sortKey="Al Amri, Sawsan S" sort="Al Amri, Sawsan S" uniqKey="Al Amri S" first="Sawsan S." last="Al-Amri">Sawsan S. Al-Amri</name></noRegion><name sortKey="Abbas, Ayman T" sort="Abbas, Ayman T" uniqKey="Abbas A" first="Ayman T." last="Abbas">Ayman T. Abbas</name><name sortKey="Al Muhanna, Muhanna K" sort="Al Muhanna, Muhanna K" uniqKey="Al Muhanna M" first="Muhanna K." last="Al-Muhanna">Muhanna K. Al-Muhanna</name><name sortKey="Alghamdi, Abrar" sort="Alghamdi, Abrar" uniqKey="Alghamdi A" first="Abrar" last="Alghamdi">Abrar Alghamdi</name><name sortKey="Alhabbab, Rowa Y" sort="Alhabbab, Rowa Y" uniqKey="Alhabbab R" first="Rowa Y." last="Alhabbab">Rowa Y. Alhabbab</name><name sortKey="Alhabbab, Rowa Y" sort="Alhabbab, Rowa Y" uniqKey="Alhabbab R" first="Rowa Y." last="Alhabbab">Rowa Y. Alhabbab</name><name sortKey="Azhar, Esam I" sort="Azhar, Esam I" uniqKey="Azhar E" first="Esam I." last="Azhar">Esam I. Azhar</name><name sortKey="Azhar, Esam I" sort="Azhar, Esam I" uniqKey="Azhar E" first="Esam I." last="Azhar">Esam I. Azhar</name><name sortKey="Hashem, Anwar M" sort="Hashem, Anwar M" uniqKey="Hashem A" first="Anwar M." last="Hashem">Anwar M. Hashem</name><name sortKey="Hashem, Anwar M" sort="Hashem, Anwar M" uniqKey="Hashem A" first="Anwar M." last="Hashem">Anwar M. Hashem</name><name sortKey="Sanki, Mohammad A" sort="Sanki, Mohammad A" uniqKey="Sanki M" first="Mohammad A." last="Sanki">Mohammad A. Sanki</name><name sortKey="Siddiq, Loai A" sort="Siddiq, Loai A" uniqKey="Siddiq L" first="Loai A." last="Siddiq">Loai A. Siddiq</name></country><country name="Égypte"><noRegion><name sortKey="Abbas, Ayman T" sort="Abbas, Ayman T" uniqKey="Abbas A" first="Ayman T." last="Abbas">Ayman T. Abbas</name></noRegion></country><country name="Canada"><noRegion><name sortKey="Li, Xuguang" sort="Li, Xuguang" uniqKey="Li X" first="Xuguang" last="Li">Xuguang Li</name></noRegion></country></tree></affiliations></record>Pour manipuler ce document sous Unix (Dilib)
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