Influenza A virus Neuraminidase as universal vaccine target

Influenza A virus (IAV) still causes significant morbidity and mortality and presents risks of pandemic outbreaks.

Seasonal vaccination mostly targeting the variable head-domain of hemagglutinin (HA) surface protein, provides only partial protection and need yearly reformulation.

There is an urgent need to identify new proteins and epitopes for universal vaccination that can provide life-long protection.

IAV Neuraminidase (NA, a second surface glycoprotein) has emerged in recent years as an attractive target for vaccination.

Importantly, NA-specific antibodies (Abs) are the best correlate of protection from IAV infection.I have a longstanding experience in studying B cell and Abs responses to IAV antigens.

In this proposal we will establish NA as universal vaccine candidate.In detail we will: 1) dissect immunogenicity and epitope specificity of Abs to NA after vaccination and immunization.

Identifying immunodominant and conserved epitopes is the first step for effective universal vaccine. 2) Test computational protein designs, based on conserved NA-epitopes, for their ability to induce protective B cells and Abs and to provide protection from heterologous IAV challenge. 3) generate bivalent alpaca nanobodies against conserved NA and HA epitopes that can provide prophylactic and therapeutic protection against shifted viruses.Overall, with this project we will identify conserved regions on NA and harness them for the development of universal influenza vaccines and therapeutics.