Audray K. Harris, Ph.D.

Schematic of structure-guided immunogen design integrated into a vaccine development pipeline. (Design) A conserved epitope from a surface antigen (green) is designed into a fusion protein in order for epitope display on a nanoparticle. Design uses bioinformatics taking into account conserved sequences and epitopes along with structural and molecular modeling of nanoparticle structures in silico. (Produce) To produce nanoparticles, protein encoding DNAs are synthesized and screened for protein expression and nanoparticle formation. (Purify) Nanoparticle production and purification is scaled for further characterization. (Characterize) Immunoassays and biophysical techniques such as electron microscopy are used. 3D structures can be produced by cryo-EM to assess particle integrity, along with epitope display and conformation. (Immunize, Challenge) Immunogenicity and challenge studies using nanoparticles as immunogens can be carried out in animal models, such as mice and ferrets with progression into human studies. Double arrows denote the general iterative nature among steps in the process of structure-guided antigen design within a vaccine pipeline.

Caption:
On the left is a 1918 H1 influenza virus-like particle (VLP) as seen by cryo-electron microscopy. On the right is the same VLP rendered in 3D with structural components computationally segmented and colored; hemagglutinin and membrane are light blue and internal components (molecular cargo) are red. 

Influenza virus particles.

EM image of spiked nanodisc structures (background) with a schematic model (foreground) showing HA complexes arranged on edge.

Using cryo-electron tomography, the laboratory of Audray K. Harris identified a novel structural display of hemagglutinin (HA). By utilizing this unique presentation of HA along the peripheral edge of a lipid membrane, this vaccine elicits more antibodies to conserved HA regions compared to other vaccine structures studied.