Development of Broadly Immunogenic and Universal Influenza Virus Vaccines

National Institute Of Allergy And Infectious Diseases

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Linked publications & trials

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 HA-based subunit vaccines 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, using electron microscopy coupled with immunoassays and animal studies we identified both structural and immunogenic differences between different commercial influenza vaccine formulations. We identified structures including individual HAs, starfish structures with up to 12 HA molecules, and novel spiked nanodisc structures that displayed over 50 HA molecules along the complex's perimeter. Vaccines containing these spiked nanodiscs elicited the highest levels of heterosubtypic cross-reactive antibodies in female mice. These results indicate that HA structural organization can be an important commercial influenza subunit vaccine parameter and can be associated with the induction of cross-reactive antibodies to conserved HA epitopes. 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.