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.
Highlights
Enveloped viruses, such as influenza, infect millions of people world-wide on an annual basis
To study the organization of virus-like particles (VLPs), they were imaged by cryo-electron microscopy
In order to answer questions about the composition and morphology of influenza virus-like particles (VLPs) and the organization and conformation of constituent hemagglutinin (HA) molecules, we studied VLPs made with the H1 HA from the 1918 influenza pandemic virus
Summary
Enveloped viruses, such as influenza, infect millions of people world-wide on an annual basis. The use of structure-guided design approaches is gaining more attention in efforts to evaluate epitope conformation and display with the goal to improve the immunogenicity and efficacy of nanoparticles for a number of viral systems[7,8,9], efforts to invoke structure-guided design of membrane containing vaccine VLPs that are pleiomorphic in structure has not been studied to a great extent. This may be because many nanoparticle platforms are refractory to structural techniques, such as X-ray crystallography, due to possible sample flexibility and pleiomorphy that impede crystallization. Influenza VLPs could be systems used to elucidate general design principles of VLP platforms for biotechnology vaccine efforts focused on viral glycoproteins
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