Investigation on the Immunogenicity of Neuraminidase and Optimization of Antigen Display for Influenza Vaccines

Abstract

Influenza viruses have co-existed with humans for centuries and continue, to this day, to cause significant health and economic burdens during yearly seasonal epidemics and especially during unpredictable pandemic years. Vaccination is the most effective measure to combat influenza and control its spread. However, the efficacy of current licensed influenza vaccines is suboptimal and varies year to year, and the process of annual reformulations and administration is cumbersome. Thus, next-generation vaccines with long-lasting and broader immune protection are urgently needed. Herein, we investigate neuraminidase (NA), the second most abundant influenza envelope glycoprotein, as a potential vaccine antigen either alone or in combination with hemagglutinin (HA) using a DNA vaccine platform. The immunogenicity of humoral responses elicited by different NA isoforms or by bivalent HA+NA vaccines in mice are our main interests. Verifying the immunogenicity of NA in DNA-based vaccines lays the groundwork for future vaccine design using other innovative vaccine technologies. In addition, we designed a HA ferritin nanoparticle capable of multivalent antigen display to enhance antigen delivery in vaccination. We report robust and specific antibody responses induced by this bioengineered nanoparticle in mice. A collaborative project is now underway to incorporate this highly immunogenic HA nanoparticle into a controlled-release polymer system to mimic traditional multi-dose vaccine regimes with a single injection. In summary, the findings of my thesis offer valuable insights into vaccine elicited immunity against NA, and the creation of multivalent nucleic acid-based influenza vaccines, and future design of vaccine with stronger protection.