Characterization of pandemic 1918 H1 hemagglutinin on influenza virus-like particles for optimizing vaccine design

Authors

• DM McCraw
• JR Gallagher
• UM Torian
• AK Harris

Abstract

Despite the availability of seasonal vaccines and antiviral medications, influenza virus continues to be a major health concern and pandemic threat due to the continually changing antigenic regions of the major surface glycoprotein, hemagglutinin (HA). Recombinant influenza virus-like particles (VLPs) are a promising vaccine platform that have been shown to elicit heterosubtypic protection against lethal challenge in animal models. However, the structure of influenza VLPs and the organization of HA molecules on the VLP surface is not fully understood. Here, we used cryo-electron microscopy and image analysis to characterize the structure of the VLPs containing HA from the 1918 pandemic. Immunoassays were used to characterize the reactivity of stem antibodies to the conserved stem region of HA in the context of VLPs. The VLPs were predominantly spherical in shape with an average width of approximately 110 nm. HA molecules were uniformly distributed on the VLP surface with an average HA-HA spacing of 8 nm. However, despite the tighter packing of the HA molecules, which are closer than HA on H1N1 viruses (~14nm), stem epitopes were accessible on VLPs. Taken together, our observations suggest that influenza H1 VLPs share a similar morphology to H1N1 viruses and that the closer arrangement of HA molecules on the VLP surface does not sterically hinder the binding of broadly neutralizing stem antibodies. Further studies of additional influenza HA subtypes incorporated into VLPs would aid in the optimization of conserved epitope display for designed immunogens towards a universal influenza vaccine that would elicit broadly neutralizing antibodies.

Scientific Focus Area: Virology

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