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Fully Human Monoclonal Antibody Directed to Proteolytic Cleavage Site in Severe Acute Respiratory Syndrome (SARS) Coronavirus S Protein Neutralizes the Virus in a Rhesus Macaque SARS Model

Identifieur interne : 002374 ( Main/Exploration ); précédent : 002373; suivant : 002375

Fully Human Monoclonal Antibody Directed to Proteolytic Cleavage Site in Severe Acute Respiratory Syndrome (SARS) Coronavirus S Protein Neutralizes the Virus in a Rhesus Macaque SARS Model

Auteurs : Tohru Miyoshi-Akiyama [Japon] ; Isao Ishida [Japon] ; Masaya Fukushi [Japon] ; Keina Yamaguchi [Japon] ; Yusuke Matsuoka [Japon] ; Takashi Ishihara [Japon] ; Masayoshi Tsukahara [Japon] ; Seisuke Hatakeyama [Japon] ; Norikazu Itoh [Japon] ; Aki Morisawa [Japon] ; Yoshiyuki Yoshinaka [Japon] ; Naoki Yamamoto [Japon] ; ZHANG LIANFENG [République populaire de Chine] ; QIN CHUAN [République populaire de Chine] ; Teruo Kirikae [Japon] ; Takehiko Sasazuki [Japon]

Source :

RBID : Pascal:11-0299481

Descripteurs français

English descriptors

Abstract

Background. There is still no effective method to prevent or treat severe acute respiratory syndrome (SARS), which is caused by SARS coronavirus (CoV). In the present study, we evaluated the efficacy of a fully human monoclonal antibody capable of neutralizing SARS-CoV in vitro in a Rhesus macaque model of SARS. Methods. The antibody 5H10 was obtained by vaccination of KM mice bearing human immunoglobulin genes with Escherichia coli-producing recombinant peptide containing the dominant epitope of the viral spike protein found in convalescent serum samples from patients with SARS. Results. 5H10, which recognized the same epitope that is also a cleavage site critical for the entry of SARS-CoV into host cells, inhibited propagation of the virus and pathological changes found in Rhesus macaques infected with the virus through the nasal route. In addition, we analyzed the mode of action of 5H10, and the results suggested that 5H10 inhibited fusion between the virus envelope and host cell membrane. 5H10 has potential for use in prevention and treatment of SARS if it reemerges. Conclusions. This study represents a platform to produce fully human antibodies against emerging infectious diseases in a timely and safe manner.


Affiliations:


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Le document en format XML

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<name sortKey="Kirikae, Teruo" sort="Kirikae, Teruo" uniqKey="Kirikae T" first="Teruo" last="Kirikae">Teruo Kirikae</name>
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<name sortKey="Sasazuki, Takehiko" sort="Sasazuki, Takehiko" uniqKey="Sasazuki T" first="Takehiko" last="Sasazuki">Takehiko Sasazuki</name>
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<title xml:lang="en" level="a">Fully Human Monoclonal Antibody Directed to Proteolytic Cleavage Site in Severe Acute Respiratory Syndrome (SARS) Coronavirus S Protein Neutralizes the Virus in a Rhesus Macaque SARS Model</title>
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<name sortKey="Miyoshi Akiyama, Tohru" sort="Miyoshi Akiyama, Tohru" uniqKey="Miyoshi Akiyama T" first="Tohru" last="Miyoshi-Akiyama">Tohru Miyoshi-Akiyama</name>
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<name sortKey="Tsukahara, Masayoshi" sort="Tsukahara, Masayoshi" uniqKey="Tsukahara M" first="Masayoshi" last="Tsukahara">Masayoshi Tsukahara</name>
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<name sortKey="Hatakeyama, Seisuke" sort="Hatakeyama, Seisuke" uniqKey="Hatakeyama S" first="Seisuke" last="Hatakeyama">Seisuke Hatakeyama</name>
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<name sortKey="Morisawa, Aki" sort="Morisawa, Aki" uniqKey="Morisawa A" first="Aki" last="Morisawa">Aki Morisawa</name>
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<name sortKey="Yoshinaka, Yoshiyuki" sort="Yoshinaka, Yoshiyuki" uniqKey="Yoshinaka Y" first="Yoshiyuki" last="Yoshinaka">Yoshiyuki Yoshinaka</name>
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</author>
<author>
<name sortKey="Yamamoto, Naoki" sort="Yamamoto, Naoki" uniqKey="Yamamoto N" first="Naoki" last="Yamamoto">Naoki Yamamoto</name>
<affiliation wicri:level="1">
<inist:fA14 i1="04">
<s1>AIDS Research Center, National Institute of Infectious Diseases</s1>
<s3>JPN</s3>
<sZ>12 aut.</sZ>
</inist:fA14>
<country>Japon</country>
<wicri:noRegion>AIDS Research Center, National Institute of Infectious Diseases</wicri:noRegion>
</affiliation>
</author>
<author>
<name sortKey="Zhang Lianfeng" sort="Zhang Lianfeng" uniqKey="Zhang Lianfeng" last="Zhang Lianfeng">ZHANG LIANFENG</name>
<affiliation wicri:level="3">
<inist:fA14 i1="07">
<s1>Institute of Laboratory Animal Science, Chinese Academy of Medical Sciences and Peking Union Medical College</s1>
<s2>Beijing</s2>
<s3>CHN</s3>
<sZ>13 aut.</sZ>
<sZ>14 aut.</sZ>
</inist:fA14>
<country>République populaire de Chine</country>
<placeName>
<settlement type="city">Pékin</settlement>
</placeName>
</affiliation>
</author>
<author>
<name sortKey="Qin Chuan" sort="Qin Chuan" uniqKey="Qin Chuan" last="Qin Chuan">QIN CHUAN</name>
<affiliation wicri:level="3">
<inist:fA14 i1="07">
<s1>Institute of Laboratory Animal Science, Chinese Academy of Medical Sciences and Peking Union Medical College</s1>
<s2>Beijing</s2>
<s3>CHN</s3>
<sZ>13 aut.</sZ>
<sZ>14 aut.</sZ>
</inist:fA14>
<country>République populaire de Chine</country>
<placeName>
<settlement type="city">Pékin</settlement>
</placeName>
</affiliation>
</author>
<author>
<name sortKey="Kirikae, Teruo" sort="Kirikae, Teruo" uniqKey="Kirikae T" first="Teruo" last="Kirikae">Teruo Kirikae</name>
<affiliation wicri:level="1">
<inist:fA14 i1="01">
<s1>Department of Infectious Diseases, National Center for Global Health and Medicine, 1-21-1</s1>
<s2>Toyama, Shinjuku-ku</s2>
<s3>JPN</s3>
<sZ>1 aut.</sZ>
<sZ>3 aut.</sZ>
<sZ>5 aut.</sZ>
<sZ>8 aut.</sZ>
<sZ>9 aut.</sZ>
<sZ>10 aut.</sZ>
<sZ>15 aut.</sZ>
</inist:fA14>
<country>Japon</country>
<wicri:noRegion>Toyama, Shinjuku-ku</wicri:noRegion>
</affiliation>
</author>
<author>
<name sortKey="Sasazuki, Takehiko" sort="Sasazuki, Takehiko" uniqKey="Sasazuki T" first="Takehiko" last="Sasazuki">Takehiko Sasazuki</name>
<affiliation wicri:level="3">
<inist:fA14 i1="05">
<s1>National Center for Global Health and Medicine, 1-21-1, Toyama</s1>
<s2>Shinjuku-ku, Tokyo</s2>
<s3>JPN</s3>
<sZ>16 aut.</sZ>
</inist:fA14>
<country>Japon</country>
<placeName>
<settlement type="city">Tokyo</settlement>
<region type="région">Région de Kantō</region>
</placeName>
</affiliation>
</author>
</analytic>
<series>
<title level="j" type="main">The Journal of infectious diseases</title>
<title level="j" type="abbreviated">J. infect. dis.</title>
<idno type="ISSN">0022-1899</idno>
<imprint>
<date when="2011">2011</date>
</imprint>
</series>
</biblStruct>
</sourceDesc>
<seriesStmt>
<title level="j" type="main">The Journal of infectious diseases</title>
<title level="j" type="abbreviated">J. infect. dis.</title>
<idno type="ISSN">0022-1899</idno>
</seriesStmt>
</fileDesc>
<profileDesc>
<textClass>
<keywords scheme="KwdEn" xml:lang="en">
<term>Cleavage site</term>
<term>Human</term>
<term>Infection</term>
<term>Macaca mulatta</term>
<term>Models</term>
<term>Monoclonal antibody</term>
<term>Protein</term>
<term>Severe acute respiratory syndrome</term>
<term>Severe acute respiratory syndrome virus</term>
</keywords>
<keywords scheme="Pascal" xml:lang="fr">
<term>Homme</term>
<term>Virus syndrome respiratoire aigu sévère</term>
<term>Macaca mulatta</term>
<term>Anticorps monoclonal</term>
<term>Site clivage</term>
<term>Protéine</term>
<term>Modèle</term>
<term>Infection</term>
<term>Syndrome respiratoire aigu sévère</term>
</keywords>
<keywords scheme="Wicri" type="topic" xml:lang="fr">
<term>Homme</term>
</keywords>
</textClass>
</profileDesc>
</teiHeader>
<front>
<div type="abstract" xml:lang="en">Background. There is still no effective method to prevent or treat severe acute respiratory syndrome (SARS), which is caused by SARS coronavirus (CoV). In the present study, we evaluated the efficacy of a fully human monoclonal antibody capable of neutralizing SARS-CoV in vitro in a Rhesus macaque model of SARS. Methods. The antibody 5H10 was obtained by vaccination of KM mice bearing human immunoglobulin genes with Escherichia coli-producing recombinant peptide containing the dominant epitope of the viral spike protein found in convalescent serum samples from patients with SARS. Results. 5H10, which recognized the same epitope that is also a cleavage site critical for the entry of SARS-CoV into host cells, inhibited propagation of the virus and pathological changes found in Rhesus macaques infected with the virus through the nasal route. In addition, we analyzed the mode of action of 5H10, and the results suggested that 5H10 inhibited fusion between the virus envelope and host cell membrane. 5H10 has potential for use in prevention and treatment of SARS if it reemerges. Conclusions. This study represents a platform to produce fully human antibodies against emerging infectious diseases in a timely and safe manner.</div>
</front>
</TEI>
<affiliations>
<list>
<country>
<li>Japon</li>
<li>République populaire de Chine</li>
</country>
<region>
<li>Région de Kantō</li>
</region>
<settlement>
<li>Pékin</li>
<li>Tokyo</li>
</settlement>
</list>
<tree>
<country name="Japon">
<noRegion>
<name sortKey="Miyoshi Akiyama, Tohru" sort="Miyoshi Akiyama, Tohru" uniqKey="Miyoshi Akiyama T" first="Tohru" last="Miyoshi-Akiyama">Tohru Miyoshi-Akiyama</name>
</noRegion>
<name sortKey="Fukushi, Masaya" sort="Fukushi, Masaya" uniqKey="Fukushi M" first="Masaya" last="Fukushi">Masaya Fukushi</name>
<name sortKey="Hatakeyama, Seisuke" sort="Hatakeyama, Seisuke" uniqKey="Hatakeyama S" first="Seisuke" last="Hatakeyama">Seisuke Hatakeyama</name>
<name sortKey="Ishida, Isao" sort="Ishida, Isao" uniqKey="Ishida I" first="Isao" last="Ishida">Isao Ishida</name>
<name sortKey="Ishihara, Takashi" sort="Ishihara, Takashi" uniqKey="Ishihara T" first="Takashi" last="Ishihara">Takashi Ishihara</name>
<name sortKey="Itoh, Norikazu" sort="Itoh, Norikazu" uniqKey="Itoh N" first="Norikazu" last="Itoh">Norikazu Itoh</name>
<name sortKey="Kirikae, Teruo" sort="Kirikae, Teruo" uniqKey="Kirikae T" first="Teruo" last="Kirikae">Teruo Kirikae</name>
<name sortKey="Matsuoka, Yusuke" sort="Matsuoka, Yusuke" uniqKey="Matsuoka Y" first="Yusuke" last="Matsuoka">Yusuke Matsuoka</name>
<name sortKey="Morisawa, Aki" sort="Morisawa, Aki" uniqKey="Morisawa A" first="Aki" last="Morisawa">Aki Morisawa</name>
<name sortKey="Sasazuki, Takehiko" sort="Sasazuki, Takehiko" uniqKey="Sasazuki T" first="Takehiko" last="Sasazuki">Takehiko Sasazuki</name>
<name sortKey="Tsukahara, Masayoshi" sort="Tsukahara, Masayoshi" uniqKey="Tsukahara M" first="Masayoshi" last="Tsukahara">Masayoshi Tsukahara</name>
<name sortKey="Yamaguchi, Keina" sort="Yamaguchi, Keina" uniqKey="Yamaguchi K" first="Keina" last="Yamaguchi">Keina Yamaguchi</name>
<name sortKey="Yamamoto, Naoki" sort="Yamamoto, Naoki" uniqKey="Yamamoto N" first="Naoki" last="Yamamoto">Naoki Yamamoto</name>
<name sortKey="Yoshinaka, Yoshiyuki" sort="Yoshinaka, Yoshiyuki" uniqKey="Yoshinaka Y" first="Yoshiyuki" last="Yoshinaka">Yoshiyuki Yoshinaka</name>
</country>
<country name="République populaire de Chine">
<noRegion>
<name sortKey="Zhang Lianfeng" sort="Zhang Lianfeng" uniqKey="Zhang Lianfeng" last="Zhang Lianfeng">ZHANG LIANFENG</name>
</noRegion>
<name sortKey="Qin Chuan" sort="Qin Chuan" uniqKey="Qin Chuan" last="Qin Chuan">QIN CHUAN</name>
</country>
</tree>
</affiliations>
</record>

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