RO1:To develop new mucosal influenza vaccine formulations based on novel adjuvant designs using nanoparticle technology.

RO2:To determine the mechanism of action, specifically dendritic and epithelial cell activation and epitope processing of successful mucosal influenza vaccines.

RO3:To identify biomarkers for immunity, long term memory and protection.

RO4: To prepare for clinical influenza vaccine trials; screening of immunogenicity in humanized mice, scaling-up production, safety and toxicity testing.

In the initial phase of the project Influenza vaccine antigen and adjuvant formulations will dominate the work in WP1. Here the aim is to develop new vaccine formulations based on the CTA1-DD vaccine adjuvant platform as well as exploring a dendritic cell targeting technique by replacing the DD-element with single-chain antibodies (ScFv) directed against DC, such as CTA1-3M2e-DEC205 and others. These constructs will then be further refined by incorporation into nanoparticle vaccine delivery vectors in WP2. Mucosal vaccine efficacy will be assessed using several approaches to nanoparticle formulation. Also, vector formulations for transcutaneous delivery will be developed and evaluated, i.e. micro-needle vaccine technology.  All the vaccine vectors and formulations will be evaluated in WP3 and WP4. The mechanistic studies in WP3 will determine various aspects on mechanism of action, such as identifying the vaccine target populations, the influence of the microbiota on vaccine efficacy, the identification of biomarkers for correlates of protection or denominators of vaccine function and the impact of long term memory and protection. The latter will be carefully monitored in WP4 where a combination of mouse, ferret and guinea pig models will guide us to identifying the best and most promising vaccine formulations for a protective mucosal pandemic influenza vaccine.  The best candidates will be brought into the clinical testing stage and preparations will be assessed for safety, toxicity and scale-up production aspects of the vaccine. Here, a humanized mouse model will be helpful to assess, at the pre-clinical stage, immunogenicity in humans.