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
Hauptverfasser: HAMELIN, Marie-Eve, COUTURE, Christian, SACKETT, Melanie, KIENER, Peter, SUZICH, Joann, ULBRANDT, Nancy, BAIVIN, Guy
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container_end_page 46
container_issue 1
container_start_page 39
container_title Antiviral therapy
container_volume 13
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
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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&lt;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&lt;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. 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Antiinfectious agents. Antiparasitic agents</topic><topic>Antibodies, Monoclonal - administration &amp; 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 &amp; 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 &amp; 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. 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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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