The prophylactic administration of a monoclonal antibody against human metapneumovirus attenuates viral disease and airways hyperresponsiveness in mice
Human metapneumovirus (hMPV) is one of the most frequent causes of respiratory tract infections in children. Our objective was to assess the prophylactic benefit of a monoclonal antibody (mAb) against the hMPV fusion protein in a murine model. BALB/c mice received one intramuscular injection of eith...
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Veröffentlicht in: | Antiviral therapy 2008, Vol.13 (1), p.39-46 |
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creator | HAMELIN, Marie-Eve COUTURE, Christian SACKETT, Melanie KIENER, Peter SUZICH, Joann ULBRANDT, Nancy BAIVIN, Guy |
description | Human metapneumovirus (hMPV) is one of the most frequent causes of respiratory tract infections in children. Our objective was to assess the prophylactic benefit of a monoclonal antibody (mAb) against the hMPV fusion protein in a murine model.
BALB/c mice received one intramuscular injection of either 5 or 10 mg/kg of mAb 338 (MedImmune, Inc.) and were infected intranasally 24 h later with 1x10(8) TCID50 (50% tissue culture infectious dose) of hMPV. On days 5 and 42 post-infection, lung samples were collected for determination of viral titres and for histopathological studies. Pulmonary function was characterized by plethysmography.
Mean lung viral titres were significantly lower in mice treated with 5 or 10 mg/kg of mAb 338 compared with infected controls on day 5 (283, 45.6 and 1.49x10(5) TCID50/g, respectively; P |
doi_str_mv | 10.1177/135965350801300104 |
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BALB/c mice received one intramuscular injection of either 5 or 10 mg/kg of mAb 338 (MedImmune, Inc.) and were infected intranasally 24 h later with 1x10(8) TCID50 (50% tissue culture infectious dose) of hMPV. On days 5 and 42 post-infection, lung samples were collected for determination of viral titres and for histopathological studies. Pulmonary function was characterized by plethysmography.
Mean lung viral titres were significantly lower in mice treated with 5 or 10 mg/kg of mAb 338 compared with infected controls on day 5 (283, 45.6 and 1.49x10(5) TCID50/g, respectively; P<0.05). Similarly, lung viral RNA copies were significantly reduced in treated mice on day 42 (292, 101 and 607 copies per 0.01 g of lungs for mice that received 5 mg/kg, 10 mg/kg or no mAb, respectively; P<0.05). Histopathological changes characterized by important alveolar and interstitial inflammation were less severe in treated mice on days 5 and 42 compared with control. Airways obstruction was also significantly reduced in both treated groups on days 5 and 42, but development of hyperresponsiveness following the acute phase of infection was only significantly reduced in 10 mg/kg treated mice.
Prophylactic administration of mAb 338 attenuates acute and late consequences of hMPV disease in this mouse model.</description><identifier>ISSN: 1359-6535</identifier><identifier>EISSN: 2040-2058</identifier><identifier>DOI: 10.1177/135965350801300104</identifier><identifier>PMID: 18389897</identifier><language>eng</language><publisher>London: International Medical Press</publisher><subject>Animals ; Antibiotics. Antiinfectious agents. Antiparasitic agents ; Antibodies, Monoclonal - administration & dosage ; Antibodies, Monoclonal - immunology ; Antibodies, Monoclonal - therapeutic use ; Antiviral agents ; Biological and medical sciences ; Bronchial Hyperreactivity - complications ; Bronchial Hyperreactivity - drug therapy ; Bronchial Hyperreactivity - prevention & control ; Bronchial Hyperreactivity - virology ; Dose-Response Relationship, Drug ; Human metapneumovirus ; Infectious diseases ; Medical sciences ; Metapneumovirus - immunology ; Mice ; Paramyxoviridae Infections - drug therapy ; Paramyxoviridae Infections - immunology ; Paramyxoviridae Infections - prevention & control ; Paramyxoviridae Infections - virology ; Pharmacology. Drug treatments ; Viral diseases</subject><ispartof>Antiviral therapy, 2008, Vol.13 (1), p.39-46</ispartof><rights>2008 INIST-CNRS</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c406t-78515029a58ad5658df9e3bad90845dd78e42f16be6b17c2cca8a278d91348863</citedby><cites>FETCH-LOGICAL-c406t-78515029a58ad5658df9e3bad90845dd78e42f16be6b17c2cca8a278d91348863</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><link.rule.ids>314,780,784,4024,27923,27924,27925</link.rule.ids><backlink>$$Uhttp://pascal-francis.inist.fr/vibad/index.php?action=getRecordDetail&idt=20158339$$DView record in Pascal Francis$$Hfree_for_read</backlink><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/18389897$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>HAMELIN, Marie-Eve</creatorcontrib><creatorcontrib>COUTURE, Christian</creatorcontrib><creatorcontrib>SACKETT, Melanie</creatorcontrib><creatorcontrib>KIENER, Peter</creatorcontrib><creatorcontrib>SUZICH, Joann</creatorcontrib><creatorcontrib>ULBRANDT, Nancy</creatorcontrib><creatorcontrib>BAIVIN, Guy</creatorcontrib><title>The prophylactic administration of a monoclonal antibody against human metapneumovirus attenuates viral disease and airways hyperresponsiveness in mice</title><title>Antiviral therapy</title><addtitle>Antivir Ther</addtitle><description>Human metapneumovirus (hMPV) is one of the most frequent causes of respiratory tract infections in children. Our objective was to assess the prophylactic benefit of a monoclonal antibody (mAb) against the hMPV fusion protein in a murine model.
BALB/c mice received one intramuscular injection of either 5 or 10 mg/kg of mAb 338 (MedImmune, Inc.) and were infected intranasally 24 h later with 1x10(8) TCID50 (50% tissue culture infectious dose) of hMPV. On days 5 and 42 post-infection, lung samples were collected for determination of viral titres and for histopathological studies. Pulmonary function was characterized by plethysmography.
Mean lung viral titres were significantly lower in mice treated with 5 or 10 mg/kg of mAb 338 compared with infected controls on day 5 (283, 45.6 and 1.49x10(5) TCID50/g, respectively; P<0.05). Similarly, lung viral RNA copies were significantly reduced in treated mice on day 42 (292, 101 and 607 copies per 0.01 g of lungs for mice that received 5 mg/kg, 10 mg/kg or no mAb, respectively; P<0.05). Histopathological changes characterized by important alveolar and interstitial inflammation were less severe in treated mice on days 5 and 42 compared with control. Airways obstruction was also significantly reduced in both treated groups on days 5 and 42, but development of hyperresponsiveness following the acute phase of infection was only significantly reduced in 10 mg/kg treated mice.
Prophylactic administration of mAb 338 attenuates acute and late consequences of hMPV disease in this mouse model.</description><subject>Animals</subject><subject>Antibiotics. Antiinfectious agents. Antiparasitic agents</subject><subject>Antibodies, Monoclonal - administration & dosage</subject><subject>Antibodies, Monoclonal - immunology</subject><subject>Antibodies, Monoclonal - therapeutic use</subject><subject>Antiviral agents</subject><subject>Biological and medical sciences</subject><subject>Bronchial Hyperreactivity - complications</subject><subject>Bronchial Hyperreactivity - drug therapy</subject><subject>Bronchial Hyperreactivity - prevention & control</subject><subject>Bronchial Hyperreactivity - virology</subject><subject>Dose-Response Relationship, Drug</subject><subject>Human metapneumovirus</subject><subject>Infectious diseases</subject><subject>Medical sciences</subject><subject>Metapneumovirus - immunology</subject><subject>Mice</subject><subject>Paramyxoviridae Infections - drug therapy</subject><subject>Paramyxoviridae Infections - immunology</subject><subject>Paramyxoviridae Infections - prevention & control</subject><subject>Paramyxoviridae Infections - virology</subject><subject>Pharmacology. Drug treatments</subject><subject>Viral diseases</subject><issn>1359-6535</issn><issn>2040-2058</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2008</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNqF0b9u1TAUBvAIgeht4QUYkBfYAv4Tx86IqkKRKrGUOTqxT7hGiR18nKI8Ca9LrnoFAwOTpaPf9w3-quqV4O-EMOa9ULprtdLccqE4F7x5Uh0kb3gtubZPq8MJ1CdxUV0Sfedc2o7z59WFsMp2tjOH6tf9EdmS03LcJnAlOAZ-DjFQyVBCiiyNDNicYnJTijAxiCUMyW8MvkGIVNhxnSGyGQssEdc5PYS8EoNSMK5QkNh-2HM-EALhnvcMQv4JG7HjtmDOSEuKFB4wIhELe1dw-KJ6NsJE-PL8XlVfP97cX9_Wd18-fb7-cFe7hrelNlYLzWUH2oLXrbZ-7FAN4DtuG-29sdjIUbQDtoMwTjoHFqSxvhOqsbZVV9Xbx979D36sSKWfAzmcJoiYVuoNb4xVpvkvlEIa0XG1Q_kIXU5EGcd-yWGGvPWC96fd-n9320Ovz-3rMKP_GzkPtYM3ZwDkYBozRBfoj5NcaKtUp34Diymj8g</recordid><startdate>2008</startdate><enddate>2008</enddate><creator>HAMELIN, Marie-Eve</creator><creator>COUTURE, Christian</creator><creator>SACKETT, Melanie</creator><creator>KIENER, Peter</creator><creator>SUZICH, Joann</creator><creator>ULBRANDT, Nancy</creator><creator>BAIVIN, Guy</creator><general>International Medical Press</general><scope>IQODW</scope><scope>CGR</scope><scope>CUY</scope><scope>CVF</scope><scope>ECM</scope><scope>EIF</scope><scope>NPM</scope><scope>AAYXX</scope><scope>CITATION</scope><scope>7U9</scope><scope>H94</scope><scope>7X8</scope></search><sort><creationdate>2008</creationdate><title>The prophylactic administration of a monoclonal antibody against human metapneumovirus attenuates viral disease and airways hyperresponsiveness in mice</title><author>HAMELIN, Marie-Eve ; COUTURE, Christian ; SACKETT, Melanie ; KIENER, Peter ; SUZICH, Joann ; ULBRANDT, Nancy ; BAIVIN, Guy</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c406t-78515029a58ad5658df9e3bad90845dd78e42f16be6b17c2cca8a278d91348863</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2008</creationdate><topic>Animals</topic><topic>Antibiotics. Antiinfectious agents. Antiparasitic agents</topic><topic>Antibodies, Monoclonal - administration & dosage</topic><topic>Antibodies, Monoclonal - immunology</topic><topic>Antibodies, Monoclonal - therapeutic use</topic><topic>Antiviral agents</topic><topic>Biological and medical sciences</topic><topic>Bronchial Hyperreactivity - complications</topic><topic>Bronchial Hyperreactivity - drug therapy</topic><topic>Bronchial Hyperreactivity - prevention & control</topic><topic>Bronchial Hyperreactivity - virology</topic><topic>Dose-Response Relationship, Drug</topic><topic>Human metapneumovirus</topic><topic>Infectious diseases</topic><topic>Medical sciences</topic><topic>Metapneumovirus - immunology</topic><topic>Mice</topic><topic>Paramyxoviridae Infections - drug therapy</topic><topic>Paramyxoviridae Infections - immunology</topic><topic>Paramyxoviridae Infections - prevention & control</topic><topic>Paramyxoviridae Infections - virology</topic><topic>Pharmacology. Drug treatments</topic><topic>Viral diseases</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>HAMELIN, Marie-Eve</creatorcontrib><creatorcontrib>COUTURE, Christian</creatorcontrib><creatorcontrib>SACKETT, Melanie</creatorcontrib><creatorcontrib>KIENER, Peter</creatorcontrib><creatorcontrib>SUZICH, Joann</creatorcontrib><creatorcontrib>ULBRANDT, Nancy</creatorcontrib><creatorcontrib>BAIVIN, Guy</creatorcontrib><collection>Pascal-Francis</collection><collection>Medline</collection><collection>MEDLINE</collection><collection>MEDLINE (Ovid)</collection><collection>MEDLINE</collection><collection>MEDLINE</collection><collection>PubMed</collection><collection>CrossRef</collection><collection>Virology and AIDS Abstracts</collection><collection>AIDS and Cancer Research Abstracts</collection><collection>MEDLINE - Academic</collection><jtitle>Antiviral therapy</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>HAMELIN, Marie-Eve</au><au>COUTURE, Christian</au><au>SACKETT, Melanie</au><au>KIENER, Peter</au><au>SUZICH, Joann</au><au>ULBRANDT, Nancy</au><au>BAIVIN, Guy</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>The prophylactic administration of a monoclonal antibody against human metapneumovirus attenuates viral disease and airways hyperresponsiveness in mice</atitle><jtitle>Antiviral therapy</jtitle><addtitle>Antivir Ther</addtitle><date>2008</date><risdate>2008</risdate><volume>13</volume><issue>1</issue><spage>39</spage><epage>46</epage><pages>39-46</pages><issn>1359-6535</issn><eissn>2040-2058</eissn><abstract>Human metapneumovirus (hMPV) is one of the most frequent causes of respiratory tract infections in children. Our objective was to assess the prophylactic benefit of a monoclonal antibody (mAb) against the hMPV fusion protein in a murine model.
BALB/c mice received one intramuscular injection of either 5 or 10 mg/kg of mAb 338 (MedImmune, Inc.) and were infected intranasally 24 h later with 1x10(8) TCID50 (50% tissue culture infectious dose) of hMPV. On days 5 and 42 post-infection, lung samples were collected for determination of viral titres and for histopathological studies. Pulmonary function was characterized by plethysmography.
Mean lung viral titres were significantly lower in mice treated with 5 or 10 mg/kg of mAb 338 compared with infected controls on day 5 (283, 45.6 and 1.49x10(5) TCID50/g, respectively; P<0.05). Similarly, lung viral RNA copies were significantly reduced in treated mice on day 42 (292, 101 and 607 copies per 0.01 g of lungs for mice that received 5 mg/kg, 10 mg/kg or no mAb, respectively; P<0.05). Histopathological changes characterized by important alveolar and interstitial inflammation were less severe in treated mice on days 5 and 42 compared with control. Airways obstruction was also significantly reduced in both treated groups on days 5 and 42, but development of hyperresponsiveness following the acute phase of infection was only significantly reduced in 10 mg/kg treated mice.
Prophylactic administration of mAb 338 attenuates acute and late consequences of hMPV disease in this mouse model.</abstract><cop>London</cop><pub>International Medical Press</pub><pmid>18389897</pmid><doi>10.1177/135965350801300104</doi><tpages>8</tpages><oa>free_for_read</oa></addata></record> |
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subjects | Animals Antibiotics. Antiinfectious agents. Antiparasitic agents Antibodies, Monoclonal - administration & dosage Antibodies, Monoclonal - immunology Antibodies, Monoclonal - therapeutic use Antiviral agents Biological and medical sciences Bronchial Hyperreactivity - complications Bronchial Hyperreactivity - drug therapy Bronchial Hyperreactivity - prevention & control Bronchial Hyperreactivity - virology Dose-Response Relationship, Drug Human metapneumovirus Infectious diseases Medical sciences Metapneumovirus - immunology Mice Paramyxoviridae Infections - drug therapy Paramyxoviridae Infections - immunology Paramyxoviridae Infections - prevention & control Paramyxoviridae Infections - virology Pharmacology. Drug treatments Viral diseases |
title | The prophylactic administration of a monoclonal antibody against human metapneumovirus attenuates viral disease and airways hyperresponsiveness in mice |
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