Project title:

Influenza causes millions of illnesses and hundreds of thousands of deaths worldwide each year, as well as placing a serious economic burden on healthcare systems. The main challenges of developing influenza vaccines is that their effectiveness, shelf life, cost-effective manufacturing, and the duration of protection provided by the currently used vaccines are limited. Furthermore, due to the rapidly changing virus strains, development and production must be adapted year after year. The aim of the project is to develop a new enhanced seasonal influenza vaccine that provides broad and lasting protection while offering robust safety profile. The development focuses on using a recombinant protein-based platform, enabling rapid adaptation in case of the emergence of new virus strains. This development is built around the following main steps and milestones: In the initial phase of basic research, recombinant production of influenza hemagglutinin virus subunits is carried out in mammalian cells to avoid egg-adapted mutations.

The partial outcome of the project is the validation and adaptation of the subunit platform to various seasonal strains. Furthermore, laboratory expression and purification of the virus subunits combined with a cellular uptake-enhancing peptide signal. In the next innovative step, we aim to demonstrate, using patented technology, the enhancement of the virus subunit cell entry efficiency and, consequently, the improvement of the induced immune response. Our goal is to examine whether the applied technology works for improved delivery of the virus subunit into human cells, with special focus on dendritic cells found in the skin, and whether the immune response can be enhanced in connection with the phenomenon of accumulation. Leveraging the excellent immunological properties of the skin, the present project aims to develop an intradermal administration method, applying modern intradermal (e.g. needle-free) technologies to facilitate dose reduction and user-friendly application. Additionally, we aim to develop a new, lyophilized (freeze-dried) formulation to improve vaccine stability (elimination of cold chain dependency) and to reduce transportation costs.

To validate the concept, early evaluation of the vaccine candidate’s efficacy (immunological tests) and safety (toxicological studies) will be conducted in a selected animal model. A dose-finding study will determine the optimal dosing range. The immunogenicity assessment will cover both the humoral (antibody production) and cellular (cytokine release) immune responses. Toxicological tests (dose toxicity, local tolerance studies) will define the safe dosing range. The successful completion of the project will have significant health and societal benefits: It may increase vaccination coverage through the user-friendly mode of administration and long shelf life at room temperature, especially in hard-to-reach regions or mobile vaccination programs. It may reduce the burden on the healthcare system caused by influenza hospitalizations, complications, and deaths, particularly among vulnerable groups. It can help improve the overall health of the population by reducing work/school absenteeism and increasing the number of active, healthy years.

The development platform may also promote biotechnology innovation and economic growth in Hungary, as it offers a marketable alternative for diversifying the global influenza vaccine supply. The project, with its novel technological approach and multidisciplinary collaboration, contributes to reducing the global public health burden of seasonal influenza.