tetano
Editor, Senior Moderator
J Virol. 2010 May 19. [Epub ahead of print]
Cross-reactive neutralizing antibodies directed against pandemic H1N1 2009 virus are protective in a highly sensitive DBA/2 influenza mouse model.
Boon AC, Debeauchamp J, Krauss S, Rubrum A, Webb AD, Webster RG, McElhaney J, Webby RJ.
Department of Infectious Diseases, St. Jude Children's Research Hospital, Memphis TN 38105, USA; Department of Medicine, University of British Columbia, Vancouver, BC, Canada.
Abstract
Our ability to rapidly respond to emerging influenza is hampered somewhat by the lack of a susceptible small animal model. To develop a more sensitive model we pathotyped eighteen low-pathogenic non-mouse-adapted influenza A viruses of human and avian origin in DBA/2 and C57BL/6 mice. The majority of the isolates (13/18) induced severe morbidity and mortality in DBA/2 mice upon intranasal challenge with one million infectious doses. Also, at a 100-fold lower dose, more than 50% of the viruses induced severe weight loss and mice succumbed to the infection. In contrast, only two virus strains were pathogenic for C57BL/6 mice upon high dose inoculation. Therefore DBA/2 mice are a suitable model to validate influenza A virus vaccines and antiviral therapies without the need for extensive viral adaptation. Correspondingly, we used the DBA/2 model to assess the level of protection afforded by pre-existing pandemic H1N1 2009 virus (H1N1pdm) cross-reactive human antibodies detected by hemagglutination inhibition assay. Passive transfer of these antibodies prior to infection protected mice from H1N1pdm-induced pathogenicity, demonstrating the effectiveness of these cross-reactive neutralizing antibodies in vivo.
PMID: 20484500 [PubMed - as supplied by publisher]
http://www.ncbi.nlm.nih.gov/pubmed/20484500?dopt=Abstract
Cross-reactive neutralizing antibodies directed against pandemic H1N1 2009 virus are protective in a highly sensitive DBA/2 influenza mouse model.
Boon AC, Debeauchamp J, Krauss S, Rubrum A, Webb AD, Webster RG, McElhaney J, Webby RJ.
Department of Infectious Diseases, St. Jude Children's Research Hospital, Memphis TN 38105, USA; Department of Medicine, University of British Columbia, Vancouver, BC, Canada.
Abstract
Our ability to rapidly respond to emerging influenza is hampered somewhat by the lack of a susceptible small animal model. To develop a more sensitive model we pathotyped eighteen low-pathogenic non-mouse-adapted influenza A viruses of human and avian origin in DBA/2 and C57BL/6 mice. The majority of the isolates (13/18) induced severe morbidity and mortality in DBA/2 mice upon intranasal challenge with one million infectious doses. Also, at a 100-fold lower dose, more than 50% of the viruses induced severe weight loss and mice succumbed to the infection. In contrast, only two virus strains were pathogenic for C57BL/6 mice upon high dose inoculation. Therefore DBA/2 mice are a suitable model to validate influenza A virus vaccines and antiviral therapies without the need for extensive viral adaptation. Correspondingly, we used the DBA/2 model to assess the level of protection afforded by pre-existing pandemic H1N1 2009 virus (H1N1pdm) cross-reactive human antibodies detected by hemagglutination inhibition assay. Passive transfer of these antibodies prior to infection protected mice from H1N1pdm-induced pathogenicity, demonstrating the effectiveness of these cross-reactive neutralizing antibodies in vivo.
PMID: 20484500 [PubMed - as supplied by publisher]
http://www.ncbi.nlm.nih.gov/pubmed/20484500?dopt=Abstract