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 subunit vaccines and 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 2022, using electron microscopy coupled with immunoassays and animal studies we identified both structural and immunogenic differences between different commercial influenza vaccines. Vaccines differed in their ability to elicit cross-reactive antibodies to antigenically different hemagglutinins (HA) not formulated in the vaccines. These results indicate that certain commercial influenza vaccines might be more advantageous in terms of pandemic preparedness. Also, we continued to design and characterize different nanoparticle platforms that display conserved epitopes from influenza HA proteins. In particular, we have biochemically and structurally studied chimeric nanoparticles carrying conserved stem epitopes from different HA subtypes displayed on the same nanoparticles. These results are expected to aid the development of more efficacious seasonal vaccines and facilitate the development of universal influenza vaccines. This work is significant and relevant to public health because influenza viruses are a large burden to human health.