Structural Biology of Influenza Epitopes

National Institute Of Allergy And Infectious Diseases

Investigators

Linked publications, trials & patents

Abstract

Influenza viruses remains a major health burden due to their abilities to change the epitopes of their major surface glycoprotein hemagglutinin. Although conserved influenza epitopes have been identified, there is a fundamental gap in understanding and correlating the disposition of conserved influenza epitopes on designed nanoparticles with immunogenicity. Lack of such information represents important problems and until they are addressed optimal display of conserved influenza epitopes cannot be understood in molecular details. In FY 2023, in the context of a collaborative project with the Vaccine Research Center (NIAID), we used cryo-electron microscopy to characterize the structure and conformation of a stabilized Hemagglutinin (HA H10) stabilized stem displayed on ferritin nanoparticles (H10ssF). In addition, we carried out molecular modelling for the H10ssF construct. The H10 stem structure was consistent with a prefusion state of HA. In addition, our laboratory used structure-guided approaches to design a novel stem nanoparticle platform consisting of the helix-A region of HA displayed on icosahedral capsid particles. We found that these designed nanoparticles were heat-stable, elicited antibodies to the HA stem, conferred protection in mouse challenge models, and showed cross-reactivity between HA subtypes. This nanoparticle platform could provide promising opportunities to improve the efficacy of influenza vaccines. This work is significant and relevant to public health because influenza viruses are a large burden to human health.