Modified vaccinia virus <scp>A</scp>nkara expressing the hemagglutinin of pandemic (<scp>H</scp>1<scp>N</scp>1) 2009 virus induces cross‐protective immunity against <scp>E</scp>urasian ‘avian‐like’ <scp>H</scp>1<scp>N</scp>1 swine viruses in mice

<jats:sec><jats:title>Objectives</jats:title><jats:p>To examine cross‐reactivity between hemagglutinin (<jats:styled-content style="fixed-case">HA</jats:styled-content>) derived from A/California/7/09 (<jats:styled-content style="fixed-case">CA</jats:styled-content>/09) virus and that derived from representative Eurasian “avian‐like” (<jats:styled-content style="fixed-case">EA</jats:styled-content>) H1N1 swine viruses isolated in Italy between 1999 and 2008 during virological surveillance in pigs.</jats:p></jats:sec><jats:sec><jats:title>Design</jats:title><jats:p>Modified vaccinia virus <jats:styled-content style="fixed-case">A</jats:styled-content>nkara (<jats:styled-content style="fixed-case">MVA</jats:styled-content>) expressing the <jats:styled-content style="fixed-case">HA</jats:styled-content> gene of <jats:styled-content style="fixed-case">CA</jats:styled-content>/09 virus (<jats:styled-content style="fixed-case">MVA</jats:styled-content>‐<jats:styled-content style="fixed-case">HA</jats:styled-content>‐<jats:styled-content style="fixed-case">CA</jats:styled-content>/09) was used as a vaccine to investigate cross‐protective immunity against H1N1 swine viruses in mice.</jats:p></jats:sec><jats:sec><jats:title>Sample</jats:title><jats:p>Two classical swine H1N1 (<jats:styled-content style="fixed-case">CS</jats:styled-content>) viruses and four representative <jats:styled-content style="fixed-case">EA</jats:styled-content>‐like H1N1 swine viruses previously isolated during outbreaks of respiratory disease in pigs on farms in Northern Italy were used in this study.</jats:p></jats:sec><jats:sec><jats:title>Setting</jats:title><jats:p>Female C57<jats:styled-content style="fixed-case">BL</jats:styled-content>/6 mice were vaccinated with <jats:styled-content style="fixed-case">MVA</jats:styled-content>/<jats:styled-content style="fixed-case">HA</jats:styled-content>/<jats:styled-content style="fixed-case">CA</jats:styled-content>/09 and then challenged intranasally with H1N1 swine viruses.</jats:p></jats:sec><jats:sec><jats:title>Main outcome measures</jats:title><jats:p>Cross‐reactive antibody responses were determined by hemagglutination‐ inhibition (<jats:styled-content style="fixed-case">HI</jats:styled-content>) and virus microneutralizing (<jats:styled-content style="fixed-case">MN</jats:styled-content>) assays of sera from <jats:styled-content style="fixed-case">MVA</jats:styled-content>‐vaccinated mice. The extent of protective immunity against infection with H1N1 swine viruses was determined by measuring lung viral load on days 2 and 4 post‐challenge.</jats:p></jats:sec><jats:sec><jats:title>Results and Conclusions</jats:title><jats:p>Systemic immunization of mice with <jats:styled-content style="fixed-case">CA</jats:styled-content>/09‐derived <jats:styled-content style="fixed-case">HA</jats:styled-content>, vectored by <jats:styled-content style="fixed-case">MVA</jats:styled-content>, elicited cross‐protective immunity against recent <jats:styled-content style="fixed-case">EA</jats:styled-content>‐like swine viruses. This immune protection was related to the levels of cross‐reactive <jats:styled-content style="fixed-case">HI</jats:styled-content> antibodies in the sera of the immunized mice and was dependent on the similarity of the antigenic site Sa of H1 <jats:styled-content style="fixed-case">HA</jats:styled-content>s. Our findings suggest that the herd immunity elicited in humans by the pandemic (H1N1) 2009 virus could limit the transmission of recent <jats:styled-content style="fixed-case">EA</jats:styled-content>‐like swine <jats:styled-content style="fixed-case">HA</jats:styled-content> genes into the influenza A virus gene pool in humans.</jats:p></jats:sec>