Off-campus UNL users: To download campus access dissertations, please use the following link to log into our proxy server with your NU ID and password. When you are done browsing please remember to return to this page and log out.

Non-UNL users: Please talk to your librarian about requesting this dissertation through interlibrary loan.

Broadly Cross-Reactive Epigraph Hemagglutinins as Universal Influenza Virus Vaccines

Brianna L Bullard, University of Nebraska - Lincoln


The substantial viral diversity of influenza virus presents a significant challenge in the development of an effective vaccine. Current influenza vaccines rely on global surveillance data to predict the future circulating virus strains of the upcoming influenza season. The immunity induced by current influenza vaccines is strain-specific and wanes rapidly, requiring yearly updates and re-administration to ensure efficacy. There is a critical need for influenza vaccines which induce long-lasting, cross-reactive immunity. Our solution is a cocktail of computationally designed hemagglutinin proteins, called Epigraph immunogens, that are designed with a bias toward potential B and T cell epitopes. We use a recombinant adenoviral (rAd) vaccine platform to deliver the Epigraph immunogens. Our initial studies used swine H3N2 (SwH3) influenza virus as a model. We found that the rAd-Epigraph SwH3 vaccine induced protective immunity in both mice and swine that was superior to a rAd-wildtype vaccine or the commercial FluSure inactivated influenza vaccine. Given the success with the SwH3 Epigraph vaccine, we designed and tested human H3N2 (HuH3) Epigraph vaccines. Again, we observed induction of superior antibody-based immunity by the HuH3 Epigraph vaccine as compared to the commercial FluZone vaccine. The HuH3 rAd-Epigraph vaccine also induced superior cellular immunity that we demonstrated to be critical in providing cross-protective immunity against historical influenza viruses. Taken together, our data shows that Epigraph immunogens provide superior immunity in comparison to wildtype immunogens. The Epigraph immunogen design strategy is a major advancement in influenza vaccine technology and, based on our promising findings, should be explored further as a universal influenza vaccine platform.

Subject Area

Molecular biology

Recommended Citation

Bullard, Brianna L, "Broadly Cross-Reactive Epigraph Hemagglutinins as Universal Influenza Virus Vaccines" (2021). ETD collection for University of Nebraska - Lincoln. AAI28413000.