Evaluation of candidate vaccine approaches for MERS-CoV
Identifieur interne : 001800 ( Main/Exploration ); précédent : 001799; suivant : 001801Evaluation of candidate vaccine approaches for MERS-CoV
Auteurs : Lingshu Wang ; Wei Shi ; M. Gordon Joyce ; Kayvon Modjarrad [États-Unis] ; Yi Zhang ; Kwanyee Leung ; Christopher R. Lees ; Tongqing Zhou ; Hadi M. Yassine ; Masaru Kanekiyo ; Zhi-Yong Yang ; Xuejun Chen ; Michelle M. Becker ; Megan Freeman ; Leatrice Vogel ; Joshua C. Johnson ; Gene Olinger ; John P. Todd ; Ulas Bagci ; Jeffrey Solomon ; Daniel J. Mollura ; Lisa Hensley ; Peter Jahrling ; Mark R. Denison ; Srinivas S. Rao ; Kanta Subbarao ; Peter D. Kwong ; John R. Mascola ; Wing-Pui Kong ; Barney S. GrahamSource :
- Nature Communications [ 2041-1723 ] ; 2015.
Descripteurs français
- KwdFr :
- ADN viral (immunologie), Animaux, Anticorps antiviraux (immunologie), Anticorps monoclonaux (immunologie), Anticorps neutralisants (immunologie), Cellules HEK293, Coronavirus du syndrome respiratoire du Moyen-Orient (immunologie), Femelle, Glycoprotéine de spicule des coronavirus (immunologie), Humains, Immunoglobuline G (immunologie), Infections à coronavirus (), Macaca mulatta, Mâle, Souris, Souris de lignée BALB C, Vaccins antiviraux (immunologie), Vaccins à ADN (immunologie).
- MESH :
- immunologie : ADN viral, Anticorps antiviraux, Anticorps monoclonaux, Anticorps neutralisants, Coronavirus du syndrome respiratoire du Moyen-Orient, Glycoprotéine de spicule des coronavirus, Immunoglobuline G, Vaccins antiviraux, Vaccins à ADN.
- Animaux, Cellules HEK293, Femelle, Humains, Infections à coronavirus, Macaca mulatta, Mâle, Souris, Souris de lignée BALB C.
English descriptors
- KwdEn :
- Animals, Antibodies, Monoclonal (immunology), Antibodies, Neutralizing (immunology), Antibodies, Viral (immunology), Coronavirus Infections (prevention & control), DNA, Viral (immunology), Female, HEK293 Cells, Humans, Immunoglobulin G (immunology), Macaca mulatta, Male, Mice, Mice, Inbred BALB C, Middle East Respiratory Syndrome Coronavirus (immunology), Spike Glycoprotein, Coronavirus (immunology), Vaccines, DNA (immunology), Viral Vaccines (immunology).
- MESH :
- chemical , immunology : Antibodies, Monoclonal, Antibodies, Neutralizing, Antibodies, Viral, DNA, Viral, Immunoglobulin G, Spike Glycoprotein, Coronavirus, Vaccines, DNA, Viral Vaccines.
- immunology : Middle East Respiratory Syndrome Coronavirus.
- prevention & control : Coronavirus Infections.
- Animals, Female, HEK293 Cells, Humans, Macaca mulatta, Male, Mice, Mice, Inbred BALB C.
Abstract
The emergence of Middle East respiratory syndrome coronavirus (MERS-CoV) as a cause of severe respiratory disease highlights the need for effective approaches to CoV vaccine development. Efforts focused solely on the receptor-binding domain (RBD) of the viral Spike (S) glycoprotein may not optimize neutralizing antibody (NAb) responses. Here we show that immunogens based on full-length S DNA and S1 subunit protein elicit robust serum-neutralizing activity against several MERS-CoV strains in mice and non-human primates. Serological analysis and isolation of murine monoclonal antibodies revealed that immunization elicits NAbs to RBD and, non-RBD portions of S1 and S2 subunit. Multiple neutralization mechanisms were demonstrated by solving the atomic structure of a NAb-RBD complex, through sequencing of neutralization escape viruses and by constructing MERS-CoV S variants for serological assays. Immunization of rhesus macaques confers protection against MERS-CoV-induced radiographic pneumonia, as assessed using computerized tomography, supporting this strategy as a promising approach for MERS-CoV vaccine development.
The online version of this article (doi:10.1038/ncomms8712) contains supplementary material, which is available to authorized users.
Url:
DOI: 10.1038/ncomms8712
PubMed: 26218507
PubMed Central: 4525294
Affiliations:
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Le document en format XML
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Bethesda, 20892 Maryland USA</nlm:aff>
<wicri:noCountry code="subfield">20892 Maryland USA</wicri:noCountry>
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<wicri:noCountry code="subfield">20892 Maryland USA</wicri:noCountry>
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<affiliation><nlm:aff id="Aff1"><institution-wrap><institution-id institution-id-type="GRID">grid.419681.3</institution-id>
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Bethesda, 20892 Maryland USA</nlm:aff>
<wicri:noCountry code="subfield">20892 Maryland USA</wicri:noCountry>
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Bethesda, 20892 Maryland USA</nlm:aff>
<wicri:noCountry code="subfield">20892 Maryland USA</wicri:noCountry>
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Bethesda, 20892 Maryland USA</nlm:aff>
<wicri:noCountry code="subfield">20892 Maryland USA</wicri:noCountry>
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<author><name sortKey="Kanekiyo, Masaru" sort="Kanekiyo, Masaru" uniqKey="Kanekiyo M" first="Masaru" last="Kanekiyo">Masaru Kanekiyo</name>
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Bethesda, 20892 Maryland USA</nlm:aff>
<wicri:noCountry code="subfield">20892 Maryland USA</wicri:noCountry>
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<wicri:noCountry code="subfield">20892 Maryland USA</wicri:noCountry>
</affiliation>
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<institution>Sanofi-Aventis, 270 Albany Street,</institution>
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Cambridge, 02139 Massachusetts USA</nlm:aff>
<wicri:noCountry code="subfield">02139 Massachusetts USA</wicri:noCountry>
</affiliation>
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<author><name sortKey="Chen, Xuejun" sort="Chen, Xuejun" uniqKey="Chen X" first="Xuejun" last="Chen">Xuejun Chen</name>
<affiliation><nlm:aff id="Aff1"><institution-wrap><institution-id institution-id-type="GRID">grid.419681.3</institution-id>
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Bethesda, 20892 Maryland USA</nlm:aff>
<wicri:noCountry code="subfield">20892 Maryland USA</wicri:noCountry>
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<institution-id institution-id-type="ISNI">0000 0004 1936 9916</institution-id>
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Nashville, 37232 Tennessee USA</nlm:aff>
<wicri:noCountry code="subfield">37232 Tennessee USA</wicri:noCountry>
</affiliation>
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<author><name sortKey="Freeman, Megan" sort="Freeman, Megan" uniqKey="Freeman M" first="Megan" last="Freeman">Megan Freeman</name>
<affiliation><nlm:aff id="Aff5"><institution-wrap><institution-id institution-id-type="GRID">grid.412807.8</institution-id>
<institution-id institution-id-type="ISNI">0000 0004 1936 9916</institution-id>
<institution>Department of Pediatrics,</institution>
<institution>Vanderbilt University Medical Center,</institution>
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Nashville, 37232 Tennessee USA</nlm:aff>
<wicri:noCountry code="subfield">37232 Tennessee USA</wicri:noCountry>
</affiliation>
</author>
<author><name sortKey="Vogel, Leatrice" sort="Vogel, Leatrice" uniqKey="Vogel L" first="Leatrice" last="Vogel">Leatrice Vogel</name>
<affiliation><nlm:aff id="Aff6"><institution-wrap><institution-id institution-id-type="GRID">grid.419681.3</institution-id>
<institution-id institution-id-type="ISNI">0000 0001 2164 9667</institution-id>
<institution>Emerging Respiratory Viruses Section, Laboratory of Infectious Diseases, National Institute of Allergy and Infectious Diseases, National Institutes of Health,</institution>
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Bethesda, 20892 Maryland USA</nlm:aff>
<wicri:noCountry code="subfield">20892 Maryland USA</wicri:noCountry>
</affiliation>
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<author><name sortKey="Johnson, Joshua C" sort="Johnson, Joshua C" uniqKey="Johnson J" first="Joshua C." last="Johnson">Joshua C. Johnson</name>
<affiliation><nlm:aff id="Aff7">Integrated Research Facility, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Frederick, 21702 Maryland USA</nlm:aff>
<wicri:noCountry code="subfield">21702 Maryland USA</wicri:noCountry>
</affiliation>
</author>
<author><name sortKey="Olinger, Gene" sort="Olinger, Gene" uniqKey="Olinger G" first="Gene" last="Olinger">Gene Olinger</name>
<affiliation><nlm:aff id="Aff7">Integrated Research Facility, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Frederick, 21702 Maryland USA</nlm:aff>
<wicri:noCountry code="subfield">21702 Maryland USA</wicri:noCountry>
</affiliation>
</author>
<author><name sortKey="Todd, John P" sort="Todd, John P" uniqKey="Todd J" first="John P." last="Todd">John P. Todd</name>
<affiliation><nlm:aff id="Aff1"><institution-wrap><institution-id institution-id-type="GRID">grid.419681.3</institution-id>
<institution-id institution-id-type="ISNI">0000 0001 2164 9667</institution-id>
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Bethesda, 20892 Maryland USA</nlm:aff>
<wicri:noCountry code="subfield">20892 Maryland USA</wicri:noCountry>
</affiliation>
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<author><name sortKey="Bagci, Ulas" sort="Bagci, Ulas" uniqKey="Bagci U" first="Ulas" last="Bagci">Ulas Bagci</name>
<affiliation><nlm:aff id="Aff8"><institution-wrap><institution-id institution-id-type="GRID">grid.94365.3d</institution-id>
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<institution>Department of Radiology and Imaging Sciences,</institution>
<institution>Center for Infectious Disease Imaging, National Institutes of Health,</institution>
</institution-wrap>
Bethesda, 20892 Maryland USA</nlm:aff>
<wicri:noCountry code="subfield">20892 Maryland USA</wicri:noCountry>
</affiliation>
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<institution>Center for Research in Computer Vision (CRCV), University of Central Florida,</institution>
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Orlando, 32816 Florida USA</nlm:aff>
<wicri:noCountry code="subfield">32816 Florida USA</wicri:noCountry>
</affiliation>
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<author><name sortKey="Solomon, Jeffrey" sort="Solomon, Jeffrey" uniqKey="Solomon J" first="Jeffrey" last="Solomon">Jeffrey Solomon</name>
<affiliation><nlm:aff id="Aff8"><institution-wrap><institution-id institution-id-type="GRID">grid.94365.3d</institution-id>
<institution-id institution-id-type="ISNI">0000 0001 2297 5165</institution-id>
<institution>Department of Radiology and Imaging Sciences,</institution>
<institution>Center for Infectious Disease Imaging, National Institutes of Health,</institution>
</institution-wrap>
Bethesda, 20892 Maryland USA</nlm:aff>
<wicri:noCountry code="subfield">20892 Maryland USA</wicri:noCountry>
</affiliation>
</author>
<author><name sortKey="Mollura, Daniel J" sort="Mollura, Daniel J" uniqKey="Mollura D" first="Daniel J." last="Mollura">Daniel J. Mollura</name>
<affiliation><nlm:aff id="Aff8"><institution-wrap><institution-id institution-id-type="GRID">grid.94365.3d</institution-id>
<institution-id institution-id-type="ISNI">0000 0001 2297 5165</institution-id>
<institution>Department of Radiology and Imaging Sciences,</institution>
<institution>Center for Infectious Disease Imaging, National Institutes of Health,</institution>
</institution-wrap>
Bethesda, 20892 Maryland USA</nlm:aff>
<wicri:noCountry code="subfield">20892 Maryland USA</wicri:noCountry>
</affiliation>
</author>
<author><name sortKey="Hensley, Lisa" sort="Hensley, Lisa" uniqKey="Hensley L" first="Lisa" last="Hensley">Lisa Hensley</name>
<affiliation><nlm:aff id="Aff7">Integrated Research Facility, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Frederick, 21702 Maryland USA</nlm:aff>
<wicri:noCountry code="subfield">21702 Maryland USA</wicri:noCountry>
</affiliation>
</author>
<author><name sortKey="Jahrling, Peter" sort="Jahrling, Peter" uniqKey="Jahrling P" first="Peter" last="Jahrling">Peter Jahrling</name>
<affiliation><nlm:aff id="Aff7">Integrated Research Facility, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Frederick, 21702 Maryland USA</nlm:aff>
<wicri:noCountry code="subfield">21702 Maryland USA</wicri:noCountry>
</affiliation>
</author>
<author><name sortKey="Denison, Mark R" sort="Denison, Mark R" uniqKey="Denison M" first="Mark R." last="Denison">Mark R. Denison</name>
<affiliation><nlm:aff id="Aff5"><institution-wrap><institution-id institution-id-type="GRID">grid.412807.8</institution-id>
<institution-id institution-id-type="ISNI">0000 0004 1936 9916</institution-id>
<institution>Department of Pediatrics,</institution>
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Nashville, 37232 Tennessee USA</nlm:aff>
<wicri:noCountry code="subfield">37232 Tennessee USA</wicri:noCountry>
</affiliation>
<affiliation><nlm:aff id="Aff10"><institution-wrap><institution-id institution-id-type="GRID">grid.412807.8</institution-id>
<institution-id institution-id-type="ISNI">0000 0004 1936 9916</institution-id>
<institution>Department of Pathology,</institution>
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Nashville, 37232 Tennessee USA</nlm:aff>
<wicri:noCountry code="subfield">37232 Tennessee USA</wicri:noCountry>
</affiliation>
</author>
<author><name sortKey="Rao, Srinivas S" sort="Rao, Srinivas S" uniqKey="Rao S" first="Srinivas S." last="Rao">Srinivas S. Rao</name>
<affiliation><nlm:aff id="Aff1"><institution-wrap><institution-id institution-id-type="GRID">grid.419681.3</institution-id>
<institution-id institution-id-type="ISNI">0000 0001 2164 9667</institution-id>
<institution>Vaccine Research Center, National Institute of Allergy and Infectious Diseases, National Institutes of Health,</institution>
</institution-wrap>
Bethesda, 20892 Maryland USA</nlm:aff>
<wicri:noCountry code="subfield">20892 Maryland USA</wicri:noCountry>
</affiliation>
</author>
<author><name sortKey="Subbarao, Kanta" sort="Subbarao, Kanta" uniqKey="Subbarao K" first="Kanta" last="Subbarao">Kanta Subbarao</name>
<affiliation><nlm:aff id="Aff6"><institution-wrap><institution-id institution-id-type="GRID">grid.419681.3</institution-id>
<institution-id institution-id-type="ISNI">0000 0001 2164 9667</institution-id>
<institution>Emerging Respiratory Viruses Section, Laboratory of Infectious Diseases, National Institute of Allergy and Infectious Diseases, National Institutes of Health,</institution>
</institution-wrap>
Bethesda, 20892 Maryland USA</nlm:aff>
<wicri:noCountry code="subfield">20892 Maryland USA</wicri:noCountry>
</affiliation>
</author>
<author><name sortKey="Kwong, Peter D" sort="Kwong, Peter D" uniqKey="Kwong P" first="Peter D." last="Kwong">Peter D. Kwong</name>
<affiliation><nlm:aff id="Aff1"><institution-wrap><institution-id institution-id-type="GRID">grid.419681.3</institution-id>
<institution-id institution-id-type="ISNI">0000 0001 2164 9667</institution-id>
<institution>Vaccine Research Center, National Institute of Allergy and Infectious Diseases, National Institutes of Health,</institution>
</institution-wrap>
Bethesda, 20892 Maryland USA</nlm:aff>
<wicri:noCountry code="subfield">20892 Maryland USA</wicri:noCountry>
</affiliation>
</author>
<author><name sortKey="Mascola, John R" sort="Mascola, John R" uniqKey="Mascola J" first="John R." last="Mascola">John R. Mascola</name>
<affiliation><nlm:aff id="Aff1"><institution-wrap><institution-id institution-id-type="GRID">grid.419681.3</institution-id>
<institution-id institution-id-type="ISNI">0000 0001 2164 9667</institution-id>
<institution>Vaccine Research Center, National Institute of Allergy and Infectious Diseases, National Institutes of Health,</institution>
</institution-wrap>
Bethesda, 20892 Maryland USA</nlm:aff>
<wicri:noCountry code="subfield">20892 Maryland USA</wicri:noCountry>
</affiliation>
</author>
<author><name sortKey="Kong, Wing Pui" sort="Kong, Wing Pui" uniqKey="Kong W" first="Wing-Pui" last="Kong">Wing-Pui Kong</name>
<affiliation><nlm:aff id="Aff1"><institution-wrap><institution-id institution-id-type="GRID">grid.419681.3</institution-id>
<institution-id institution-id-type="ISNI">0000 0001 2164 9667</institution-id>
<institution>Vaccine Research Center, National Institute of Allergy and Infectious Diseases, National Institutes of Health,</institution>
</institution-wrap>
Bethesda, 20892 Maryland USA</nlm:aff>
<wicri:noCountry code="subfield">20892 Maryland USA</wicri:noCountry>
</affiliation>
</author>
<author><name sortKey="Graham, Barney S" sort="Graham, Barney S" uniqKey="Graham B" first="Barney S." last="Graham">Barney S. Graham</name>
<affiliation><nlm:aff id="Aff1"><institution-wrap><institution-id institution-id-type="GRID">grid.419681.3</institution-id>
<institution-id institution-id-type="ISNI">0000 0001 2164 9667</institution-id>
<institution>Vaccine Research Center, National Institute of Allergy and Infectious Diseases, National Institutes of Health,</institution>
</institution-wrap>
Bethesda, 20892 Maryland USA</nlm:aff>
<wicri:noCountry code="subfield">20892 Maryland USA</wicri:noCountry>
</affiliation>
</author>
</analytic>
<series><title level="j">Nature Communications</title>
<idno type="eISSN">2041-1723</idno>
<imprint><date when="2015">2015</date>
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<term>Antibodies, Neutralizing (immunology)</term>
<term>Antibodies, Viral (immunology)</term>
<term>Coronavirus Infections (prevention & control)</term>
<term>DNA, Viral (immunology)</term>
<term>Female</term>
<term>HEK293 Cells</term>
<term>Humans</term>
<term>Immunoglobulin G (immunology)</term>
<term>Macaca mulatta</term>
<term>Male</term>
<term>Mice</term>
<term>Mice, Inbred BALB C</term>
<term>Middle East Respiratory Syndrome Coronavirus (immunology)</term>
<term>Spike Glycoprotein, Coronavirus (immunology)</term>
<term>Vaccines, DNA (immunology)</term>
<term>Viral Vaccines (immunology)</term>
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<term>Antibodies, Neutralizing</term>
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<term>DNA, Viral</term>
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<term>Spike Glycoprotein, Coronavirus</term>
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<term>Viral Vaccines</term>
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<keywords scheme="MESH" qualifier="immunology" xml:lang="en"><term>Middle East Respiratory Syndrome Coronavirus</term>
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<term>Female</term>
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<term>Humans</term>
<term>Macaca mulatta</term>
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<term>Mice, Inbred BALB C</term>
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<term>Femelle</term>
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<term>Infections à coronavirus</term>
<term>Macaca mulatta</term>
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<front><div type="abstract" xml:lang="en"><p id="Par1">The emergence of Middle East respiratory syndrome coronavirus (MERS-CoV) as a cause of severe respiratory disease highlights the need for effective approaches to CoV vaccine development. Efforts focused solely on the receptor-binding domain (RBD) of the viral Spike (S) glycoprotein may not optimize neutralizing antibody (NAb) responses. Here we show that immunogens based on full-length S DNA and S1 subunit protein elicit robust serum-neutralizing activity against several MERS-CoV strains in mice and non-human primates. Serological analysis and isolation of murine monoclonal antibodies revealed that immunization elicits NAbs to RBD and, non-RBD portions of S1 and S2 subunit. Multiple neutralization mechanisms were demonstrated by solving the atomic structure of a NAb-RBD complex, through sequencing of neutralization escape viruses and by constructing MERS-CoV S variants for serological assays. Immunization of rhesus macaques confers protection against MERS-CoV-induced radiographic pneumonia, as assessed using computerized tomography, supporting this strategy as a promising approach for MERS-CoV vaccine development.</p>
<sec><title>Supplementary information</title>
<p>The online version of this article (doi:10.1038/ncomms8712) contains supplementary material, which is available to authorized users.</p>
</sec>
</div>
</front>
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