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Protection of mammalian cells from severe acute respiratory syndrome coronavirus infection by equine neutralizing antibody.

Identifieur interne : 002566 ( PubMed/Checkpoint ); précédent : 002565; suivant : 002567

Protection of mammalian cells from severe acute respiratory syndrome coronavirus infection by equine neutralizing antibody.

Auteurs : Xiliang Wang [République populaire de Chine] ; Bing Ni ; Xinan Du ; Guangyu Zhao ; Wenda Gao ; Xinfu Shi ; Songle Zhang ; Liangyan Zhang ; Dong Wang ; Deyan Luo ; Li Xing ; Haiyan Jiang ; Wanling Li ; Man Jiang ; Liwei Mao ; Yangdong He ; Yu Xiao ; Yuzhang Wu

Source :

RBID : pubmed:16152762

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English descriptors

Abstract

The aetiological agent for severe acute respiratory syndrome (SARS) has been determined to be a new type of coronavirus (SARS-CoV) that infects a wide range of mammalian hosts. Up to now, there have been no specific drugs to protect against SARS-CoV infection, thus developing effective strategies against this newly emerged viral infection warrants urgent efforts. Adoptive immune therapy with pathogen-specific heterologous immunoglobulin has been successfully used to control the dissemination of many viral infections. To investigate whether a neutralizing antibody against SARS-CoV raised in an artiodactylous host can have a protective role on primate cells, we prepared serum IgGs and their pepsin-digested F(ab')2 fragments from horses inoculated with purified SARS-CoV (BJ-01 strain). The protective effect of the F(ab')2 fragments against SARS-CoV infection was determined in cultured Vero E6 cells by cytopathic effect (CPE), MTT and plaque-forming assays and in a Balb/c mouse model by CPE and quantitative RT-PCR. The results showed the neutralization titres of F(ab')2 from three horses all reached at least 1:1600, and 50 microg of the F(ab')2 fragments could completely neutralize 1x10(4) TCID50- SARS-CoV in vivo. Additionally, we observed that F(ab')2, against BJ-01 strain could also protect cells from infection by the variant GZ-01 strain in vitro and in vivo. Our work has provided experimental support for testing the protective equine immunoglobulin in future large primate or human trials.

PubMed: 16152762


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pubmed:16152762

Le document en format XML

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<div type="abstract" xml:lang="en">The aetiological agent for severe acute respiratory syndrome (SARS) has been determined to be a new type of coronavirus (SARS-CoV) that infects a wide range of mammalian hosts. Up to now, there have been no specific drugs to protect against SARS-CoV infection, thus developing effective strategies against this newly emerged viral infection warrants urgent efforts. Adoptive immune therapy with pathogen-specific heterologous immunoglobulin has been successfully used to control the dissemination of many viral infections. To investigate whether a neutralizing antibody against SARS-CoV raised in an artiodactylous host can have a protective role on primate cells, we prepared serum IgGs and their pepsin-digested F(ab')2 fragments from horses inoculated with purified SARS-CoV (BJ-01 strain). The protective effect of the F(ab')2 fragments against SARS-CoV infection was determined in cultured Vero E6 cells by cytopathic effect (CPE), MTT and plaque-forming assays and in a Balb/c mouse model by CPE and quantitative RT-PCR. The results showed the neutralization titres of F(ab')2 from three horses all reached at least 1:1600, and 50 microg of the F(ab')2 fragments could completely neutralize 1x10(4) TCID50- SARS-CoV in vivo. Additionally, we observed that F(ab')2, against BJ-01 strain could also protect cells from infection by the variant GZ-01 strain in vitro and in vivo. Our work has provided experimental support for testing the protective equine immunoglobulin in future large primate or human trials.</div>
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<AbstractText>The aetiological agent for severe acute respiratory syndrome (SARS) has been determined to be a new type of coronavirus (SARS-CoV) that infects a wide range of mammalian hosts. Up to now, there have been no specific drugs to protect against SARS-CoV infection, thus developing effective strategies against this newly emerged viral infection warrants urgent efforts. Adoptive immune therapy with pathogen-specific heterologous immunoglobulin has been successfully used to control the dissemination of many viral infections. To investigate whether a neutralizing antibody against SARS-CoV raised in an artiodactylous host can have a protective role on primate cells, we prepared serum IgGs and their pepsin-digested F(ab')2 fragments from horses inoculated with purified SARS-CoV (BJ-01 strain). The protective effect of the F(ab')2 fragments against SARS-CoV infection was determined in cultured Vero E6 cells by cytopathic effect (CPE), MTT and plaque-forming assays and in a Balb/c mouse model by CPE and quantitative RT-PCR. The results showed the neutralization titres of F(ab')2 from three horses all reached at least 1:1600, and 50 microg of the F(ab')2 fragments could completely neutralize 1x10(4) TCID50- SARS-CoV in vivo. Additionally, we observed that F(ab')2, against BJ-01 strain could also protect cells from infection by the variant GZ-01 strain in vitro and in vivo. Our work has provided experimental support for testing the protective equine immunoglobulin in future large primate or human trials.</AbstractText>
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