tetano
Editor, Senior Moderator
Clin Vaccine Immunol. 2016 Apr 13. pii: CVI.00085-16. [Epub ahead of print]
Characterization of influenza vaccine hemagglutinin complexes by cryo-electron microscopy and image analyses reveals structural polymorphisms.
McCraw DM[SUP]1[/SUP], Gallagher JR[SUP]1[/SUP], Harris AK[SUP]2[/SUP].
Author information
Abstract
Influenza virus afflicts millions of people worldwide on an annual basis. There is the ever-present threat of animal viruses crossing the species barrier to cause epidemics and pandemics resulting in great morbidity and mortality. Zoonosis outbreaks such as H7N9 underscore the need to better understand the molecular organization of viral immunogens such as recombinant influenza hemagglutinin (HA) proteins used in influenza subunit vaccines in order to optimize vaccine efficacy. Here we show using cryo-electron microscopy and image analysis that vaccine recombinant H7 HA form macromolecular complexes consisting of a variable number of HA subunits (6 to 8). In addition, HA-complexes were distributed across at least four distinct structural classes (polymorphisms). 3D reconstruction and molecular modeling indicated that HA was in the pre-fusion state and suggested that the mechanism for oligomerization and observed structural polymorphisms were due to hydrophobic interactions involving the transmembrane regions. These experiments suggest that characterization of the molecular structures of influenza HA complexes used in subunit vaccines will lead to further understanding of the differences in vaccine efficacy and future optimization of subunit vaccines to prevent influenza infection.
Copyright ? 2016 McCraw et al.
PMID: 27074939 [PubMed - as supplied by publisher]
Characterization of influenza vaccine hemagglutinin complexes by cryo-electron microscopy and image analyses reveals structural polymorphisms.
McCraw DM[SUP]1[/SUP], Gallagher JR[SUP]1[/SUP], Harris AK[SUP]2[/SUP].
Author information
Abstract
Influenza virus afflicts millions of people worldwide on an annual basis. There is the ever-present threat of animal viruses crossing the species barrier to cause epidemics and pandemics resulting in great morbidity and mortality. Zoonosis outbreaks such as H7N9 underscore the need to better understand the molecular organization of viral immunogens such as recombinant influenza hemagglutinin (HA) proteins used in influenza subunit vaccines in order to optimize vaccine efficacy. Here we show using cryo-electron microscopy and image analysis that vaccine recombinant H7 HA form macromolecular complexes consisting of a variable number of HA subunits (6 to 8). In addition, HA-complexes were distributed across at least four distinct structural classes (polymorphisms). 3D reconstruction and molecular modeling indicated that HA was in the pre-fusion state and suggested that the mechanism for oligomerization and observed structural polymorphisms were due to hydrophobic interactions involving the transmembrane regions. These experiments suggest that characterization of the molecular structures of influenza HA complexes used in subunit vaccines will lead to further understanding of the differences in vaccine efficacy and future optimization of subunit vaccines to prevent influenza infection.
Copyright ? 2016 McCraw et al.
PMID: 27074939 [PubMed - as supplied by publisher]