tetano
Editor, Senior Moderator
PLoS One. 2015 Jun 10;10(6):e0127649. doi: 10.1371/journal.pone.0127649. eCollection 2015.
[h=1]Construction and Immunogenicity Evaluation of Recombinant Influenza A Viruses Containing Chimeric Hemagglutinin Genes Derived from Genetically Divergent Influenza A H1N1 Subtype Viruses.[/h] McCormick K[SUP]1[/SUP], Jiang Z[SUP]2[/SUP], Zhu L[SUP]2[/SUP], Lawson SR[SUP]2[/SUP], Langenhorst R[SUP]2[/SUP], Ransburgh R[SUP]2[/SUP], Brunick C[SUP]1[/SUP], Tracy MC[SUP]1[/SUP], Hurtig HR[SUP]1[/SUP], Mabee LM[SUP]1[/SUP], Mingo M[SUP]1[/SUP], Li Y[SUP]2[/SUP], Webby RJ[SUP]3[/SUP], Huber VC[SUP]1[/SUP], Fang Y[SUP]2[/SUP].
[h=3]Author information[/h]
[h=3]Abstract[/h] [h=4]BACKGROUND AND OBJECTIVES:[/h] Influenza A viruses cause highly contagious diseases in a variety of hosts, including humans and pigs. To develop a vaccine that can be broadly effective against genetically divergent strains of the virus, in this study we employed molecular breeding (DNA shuffling) technology to create a panel of chimeric HA genes.
[h=4]METHODS AND RESULTS:[/h] Each chimeric HA gene contained genetic elements from parental swine influenza A viruses that had a history of zoonotic transmission, and also from a 2009 pandemic virus. Each parental virus represents a major phylogenetic clade of influenza A H1N1 viruses. Nine shuffled HA constructs were initially screened for immunogenicity in mice by DNA immunization, and one chimeric HA (HA-129) was expressed on both a A/Puerto Rico/8/34 backbone with mutations associated with a live, attenuated phenotype (PR8LAIV-129) and a A/swine/Texas/4199-2/98 backbone (TX98-129). When delivered to mice, the PR8LAIV-129 induced antibodies against all four parental viruses, which was similar to the breadth of immunity observed when HA-129 was delivered as a DNA vaccine. This chimeric HA was then tested as a candidate vaccine in a nursery pig model, using inactivated TX98-129 virus as the backbone. The results demonstrate that pigs immunized with HA-129 developed antibodies against all four parental viruses, as well as additional primary swine H1N1 influenza virus field isolates.
[h=4]CONCLUSION:[/h] This study established a platform for creating novel genes of influenza viruses using a molecular breeding approach, which will have important applications toward future development of broadly protective influenza virus vaccines.
PMID: 26061265 [PubMed - in process] Free full text
[h=1]Construction and Immunogenicity Evaluation of Recombinant Influenza A Viruses Containing Chimeric Hemagglutinin Genes Derived from Genetically Divergent Influenza A H1N1 Subtype Viruses.[/h] McCormick K[SUP]1[/SUP], Jiang Z[SUP]2[/SUP], Zhu L[SUP]2[/SUP], Lawson SR[SUP]2[/SUP], Langenhorst R[SUP]2[/SUP], Ransburgh R[SUP]2[/SUP], Brunick C[SUP]1[/SUP], Tracy MC[SUP]1[/SUP], Hurtig HR[SUP]1[/SUP], Mabee LM[SUP]1[/SUP], Mingo M[SUP]1[/SUP], Li Y[SUP]2[/SUP], Webby RJ[SUP]3[/SUP], Huber VC[SUP]1[/SUP], Fang Y[SUP]2[/SUP].
[h=3]Author information[/h]
[h=3]Abstract[/h] [h=4]BACKGROUND AND OBJECTIVES:[/h] Influenza A viruses cause highly contagious diseases in a variety of hosts, including humans and pigs. To develop a vaccine that can be broadly effective against genetically divergent strains of the virus, in this study we employed molecular breeding (DNA shuffling) technology to create a panel of chimeric HA genes.
[h=4]METHODS AND RESULTS:[/h] Each chimeric HA gene contained genetic elements from parental swine influenza A viruses that had a history of zoonotic transmission, and also from a 2009 pandemic virus. Each parental virus represents a major phylogenetic clade of influenza A H1N1 viruses. Nine shuffled HA constructs were initially screened for immunogenicity in mice by DNA immunization, and one chimeric HA (HA-129) was expressed on both a A/Puerto Rico/8/34 backbone with mutations associated with a live, attenuated phenotype (PR8LAIV-129) and a A/swine/Texas/4199-2/98 backbone (TX98-129). When delivered to mice, the PR8LAIV-129 induced antibodies against all four parental viruses, which was similar to the breadth of immunity observed when HA-129 was delivered as a DNA vaccine. This chimeric HA was then tested as a candidate vaccine in a nursery pig model, using inactivated TX98-129 virus as the backbone. The results demonstrate that pigs immunized with HA-129 developed antibodies against all four parental viruses, as well as additional primary swine H1N1 influenza virus field isolates.
[h=4]CONCLUSION:[/h] This study established a platform for creating novel genes of influenza viruses using a molecular breeding approach, which will have important applications toward future development of broadly protective influenza virus vaccines.
PMID: 26061265 [PubMed - in process] Free full text