RESUMO
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.
Assuntos
Anticorpos Neutralizantes/imunologia , Anticorpos Antivirais/imunologia , Proteção Cruzada , Reações Cruzadas , Vírus da Influenza A Subtipo H1N1/imunologia , Infecções por Orthomyxoviridae/prevenção & controle , Animais , Anticorpos Neutralizantes/uso terapêutico , Anticorpos Antivirais/uso terapêutico , Peso Corporal , Modelos Animais de Doenças , Feminino , Testes de Inibição da Hemaglutinação , Humanos , Imunização Passiva , Camundongos , Camundongos Endogâmicos C57BL , Camundongos Endogâmicos DBA , Infecções por Orthomyxoviridae/mortalidade , Infecções por Orthomyxoviridae/patologia , Análise de SobrevidaRESUMO
Levels of preexisting antibodies to the hemagglutinin of pandemic influenza A(H1N1) 2009 (hereafter pandemic H1N1) virus positively correlate with age. The impact of contemporary seasonal influenza vaccines on establishing immunity to other pandemic H1N1 proteins is unknown. We measured serum antibodies to the neuraminidase (NA) of pandemic H1N1 in adults prior to and after vaccination with seasonal trivalent inactivated influenza vaccines. Serum antibodies to pandemic H1N1 NA were observed in all age groups; however, vaccination elevated levels of pandemic H1N1 NA antibodies predominately in elderly individuals (age, ⩾60 years). Therefore, contemporary seasonal vaccines likely contribute to reduction of pandemic H1N1-associated disease in older individuals.