Cross-reactive neutralizing antibodies directed against pandemic H1N1 2009 virus are protective in a highly sensitive DBA/2 mouse influenza model.
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 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 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.
Boon
Adrianus C M
AC
Department of Infectious Diseases, St. Jude Children's Research Hospital, Memphis, Tennessee 38105, USA.
deBeauchamp
Jennifer
J
Krauss
Scott
S
Rubrum
Adam
A
Webb
Ashley D
AD
Webster
Robert G
RG
McElhaney
Janet
J
Webby
Richard J
RJ
D000818:Animals; D057134:Antibodies, Neutralizing / Q000276:immunology* / Q000627:therapeutic use; D000914:Antibodies, Viral / Q000276:immunology* / Q000627:therapeutic use; D001835:Body Weight; D056738:Cross Protection; D003429:Cross Reactions; D004195:Disease Models, Animal; D005260:Female; D006385:Hemagglutination Inhibition Tests; D006801:Humans; D007116:Immunization, Passive; D053118:Influenza A Virus, H1N1 Subtype / Q000276:immunology*; D051379:Mice; D008810:Mice, Inbred C57BL; D008811:Mice, Inbred DBA; D009976:Orthomyxoviridae Infections / Q000401:mortality / Q000473:pathology / Q000517:prevention & control*; D016019:Survival Analysis
D057134:Antibodies, Neutralizing; D000914:Antibodies, Viral