Cross-reactive neutralizing antibodies directed against pandemic H1N1 2009 virus are protective in a highly sensitive DBA/2 mouse influenza model

Adrianus C.M. Boon, Jennifer DeBeauchamp, Scott Krauss, Adam Rubrum, Ashley D. Webb, Robert G. Webster, Janet McElhaney, Richard J. Webby

Research output: Contribution to journalArticle

50 Scopus citations

Abstract

Our ability to rapidly respond to an emerging influenza pandemic is hampered somewhat by the lack of a susceptible small-animal model. To develop a more sensitive model, we pathotyped 18 low-pathogenic nonmouse-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 1 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 preexisting pandemic H1N1 2009 virus (H1N1pdm) cross-reactive human antibodies detected by a 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.

Original languageEnglish
Pages (from-to)7662-7667
Number of pages6
JournalJournal of virology
Volume84
Issue number15
DOIs
StatePublished - Aug 1 2010
Externally publishedYes

Fingerprint Dive into the research topics of 'Cross-reactive neutralizing antibodies directed against pandemic H1N1 2009 virus are protective in a highly sensitive DBA/2 mouse influenza model'. Together they form a unique fingerprint.

  • Cite this