Serveur d'exploration MERS

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One-Health: a Safe, Efficient, Dual-Use Vaccine for Humans and Animals against Middle East Respiratory Syndrome Coronavirus and Rabies Virus.

Identifieur interne : 000C54 ( Main/Exploration ); précédent : 000C53; suivant : 000C55

One-Health: a Safe, Efficient, Dual-Use Vaccine for Humans and Animals against Middle East Respiratory Syndrome Coronavirus and Rabies Virus.

Auteurs : Christoph Wirblich [États-Unis] ; Christopher M. Coleman [États-Unis] ; Drishya Kurup [États-Unis] ; Tara S. Abraham [États-Unis] ; John G. Bernbaum [États-Unis] ; Peter B. Jahrling [États-Unis] ; Lisa E. Hensley [États-Unis] ; Reed F. Johnson [États-Unis] ; Matthew B. Frieman [États-Unis] ; Matthias J. Schnell [États-Unis]

Source :

RBID : pubmed:27807241

Descripteurs français

English descriptors

Abstract

Middle East respiratory syndrome coronavirus (MERS-CoV) emerged in 2012 and is a highly pathogenic respiratory virus. There are no treatment options against MERS-CoV for humans or animals, and there are no large-scale clinical trials for therapies against MERS-CoV. To address this need, we developed an inactivated rabies virus (RABV) that contains the MERS-CoV spike (S) protein expressed on its surface. Our initial recombinant vaccine, BNSP333-S, expresses a full-length wild-type MERS-CoV S protein; however, it showed significantly reduced viral titers compared to those of the parental RABV strain and only low-level incorporation of full-length MERS-CoV S into RABV particles. Therefore, we developed a RABV-MERS vector that contained the MERS-CoV S1 domain of the MERS-CoV S protein fused to the RABV G protein C terminus (BNSP333-S1). BNSP333-S1 grew to titers similar to those of the parental vaccine vector BNSP333, and the RABV G-MERS-CoV S1 fusion protein was efficiently expressed and incorporated into RABV particles. When we vaccinated mice, chemically inactivated BNSP333-S1 induced high-titer neutralizing antibodies. Next, we challenged both vaccinated mice and control mice with MERS-CoV after adenovirus transduction of the human dipeptidyl peptidase 4 (hDPP4) receptor and then analyzed the ability of mice to control MERS-CoV infection. Our results demonstrated that vaccinated mice were fully protected from the MERS-CoV challenge, as indicated by the significantly lower MERS-CoV titers and MERS-CoV and mRNA levels in challenged mice than those in unvaccinated controls. These data establish that an inactivated RABV-MERS S-based vaccine may be effective for use in animals and humans in areas where MERS-CoV is endemic.

DOI: 10.1128/JVI.02040-16
PubMed: 27807241


Affiliations:


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Le document en format XML

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<front>
<div type="abstract" xml:lang="en">Middle East respiratory syndrome coronavirus (MERS-CoV) emerged in 2012 and is a highly pathogenic respiratory virus. There are no treatment options against MERS-CoV for humans or animals, and there are no large-scale clinical trials for therapies against MERS-CoV. To address this need, we developed an inactivated rabies virus (RABV) that contains the MERS-CoV spike (S) protein expressed on its surface. Our initial recombinant vaccine, BNSP333-S, expresses a full-length wild-type MERS-CoV S protein; however, it showed significantly reduced viral titers compared to those of the parental RABV strain and only low-level incorporation of full-length MERS-CoV S into RABV particles. Therefore, we developed a RABV-MERS vector that contained the MERS-CoV S1 domain of the MERS-CoV S protein fused to the RABV G protein C terminus (BNSP333-S1). BNSP333-S1 grew to titers similar to those of the parental vaccine vector BNSP333, and the RABV G-MERS-CoV S1 fusion protein was efficiently expressed and incorporated into RABV particles. When we vaccinated mice, chemically inactivated BNSP333-S1 induced high-titer neutralizing antibodies. Next, we challenged both vaccinated mice and control mice with MERS-CoV after adenovirus transduction of the human dipeptidyl peptidase 4 (hDPP4) receptor and then analyzed the ability of mice to control MERS-CoV infection. Our results demonstrated that vaccinated mice were fully protected from the MERS-CoV challenge, as indicated by the significantly lower MERS-CoV titers and MERS-CoV and mRNA levels in challenged mice than those in unvaccinated controls. These data establish that an inactivated RABV-MERS S-based vaccine may be effective for use in animals and humans in areas where MERS-CoV is endemic.</div>
</front>
</TEI>
<affiliations>
<list>
<country>
<li>États-Unis</li>
</country>
<region>
<li>Maryland</li>
<li>Pennsylvanie</li>
</region>
</list>
<tree>
<country name="États-Unis">
<region name="Pennsylvanie">
<name sortKey="Wirblich, Christoph" sort="Wirblich, Christoph" uniqKey="Wirblich C" first="Christoph" last="Wirblich">Christoph Wirblich</name>
</region>
<name sortKey="Abraham, Tara S" sort="Abraham, Tara S" uniqKey="Abraham T" first="Tara S" last="Abraham">Tara S. Abraham</name>
<name sortKey="Bernbaum, John G" sort="Bernbaum, John G" uniqKey="Bernbaum J" first="John G" last="Bernbaum">John G. Bernbaum</name>
<name sortKey="Coleman, Christopher M" sort="Coleman, Christopher M" uniqKey="Coleman C" first="Christopher M" last="Coleman">Christopher M. Coleman</name>
<name sortKey="Frieman, Matthew B" sort="Frieman, Matthew B" uniqKey="Frieman M" first="Matthew B" last="Frieman">Matthew B. Frieman</name>
<name sortKey="Hensley, Lisa E" sort="Hensley, Lisa E" uniqKey="Hensley L" first="Lisa E" last="Hensley">Lisa E. Hensley</name>
<name sortKey="Jahrling, Peter B" sort="Jahrling, Peter B" uniqKey="Jahrling P" first="Peter B" last="Jahrling">Peter B. Jahrling</name>
<name sortKey="Johnson, Reed F" sort="Johnson, Reed F" uniqKey="Johnson R" first="Reed F" last="Johnson">Reed F. Johnson</name>
<name sortKey="Kurup, Drishya" sort="Kurup, Drishya" uniqKey="Kurup D" first="Drishya" last="Kurup">Drishya Kurup</name>
<name sortKey="Schnell, Matthias J" sort="Schnell, Matthias J" uniqKey="Schnell M" first="Matthias J" last="Schnell">Matthias J. Schnell</name>
</country>
</tree>
</affiliations>
</record>

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