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Structural analysis of influenza vaccine virus-like particles reveals a multicomponent organization

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  • Structural analysis of influenza vaccine virus-like particles reveals a multicomponent organization

    Sci Rep. 2018 Jul 9;8(1):10342. doi: 10.1038/s41598-018-28700-7.
    Structural analysis of influenza vaccine virus-like particles reveals a multicomponent organization.

    McCraw DM1, Gallagher JR1, Torian U1, Myers ML1, Conlon MT1, Gulati NM1, Harris AK2.
    Author information

    Abstract

    Influenza virus continues to be a major health problem due to the continually changing immunodominant head regions of the major surface glycoprotein, hemagglutinin (HA). However, some emerging vaccine platforms designed by biotechnology efforts, such as recombinant influenza virus-like particles (VLPs) have been shown to elicit protective antibodies to antigenically different influenza viruses. Here, using biochemical analyses and cryo-electron microscopy methods coupled to image analysis, we report the composition and 3D structural organization of influenza VLPs of the 1918 pandemic influenza virus. HA molecules were uniformly distributed on the VLP surfaces and the conformation of HA was in a prefusion state. Moreover, HA could be bound by antibody targeting conserved epitopes in the stem region of HA. Taken together, our analysis suggests structural parameters that may be important for VLP biotechnology such as a multi-component organization with (i) an outer component consisting of prefusion HA spikes on the surfaces, (ii) a VLP membrane with HA distribution permitting stem epitope display, and (iii) internal structural components.


    PMID: 29985483 DOI: 10.1038/s41598-018-28700-7
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