From airway immunity to influenza vaccine design

Seasonal influenza causes significant morbidity and mortality every year, with the possibility of global pandemic outbreaks. Current vaccines provide reasonable protection against circulating viruses but require yearly reformulation. Therefore, there is an urgent need to develop a vaccine that could provide long term immunity to the virus. Our work aims at defining the basic immunological mechanisms of antibody and B cell responses as an essential step towards an effective universal vaccination.

Projects in our group broadly address two aspects of antiviral immunity: 1) mucosal immune responses in the upper respiratory tract and 2) development of new vaccines and therapeutics against influenza infection. We combine in vivo and in vitro studies, using a range of immunological techniques, multicolor flow cytometry and single cell sequencing in order to address these questions.

Mucosal immune responses in the upper respiratory tract: Influenza A Virus primarily replicates in the upper and lower respiratory tract. In recent years, tissue resident memory B cells (BRM) were shown to be established in the lungs after infection. These cells rapidly reactivate after re-infection to differentiate to antibody secreting cells. In the lab we address several gaps of knowledge in airways immunology: ongoing projects aim at defining the exact factors required for lung BRM formation and maintenance. A strong focus of the laboratory is also on adaptive immunity in the upper respiratory tract, including nasal tissue and NALT. Immunology in the nasal tissue is almost uncharted territory and our current projects aim at investigating B and CD4 T cell dynamics in this niche.

Development of new vaccines and therapeutics: in the lab we collaborate with world leading laboratories to effectively design and test novel vaccines and therapeutics. Current projects include the computational design of immunogens that mimic epitopes of broadly-neutralizing anti-influenza antibodies. In addition, we have isolated a nanobody specific for the avian influenza strain H7N9 and discovered that this nanobody was also able to cross-recognize and cross-protect against several viral variants similar to the ones circulating in humans. Work continues in order to identify how to target portion of the virus that are conserved across several viral strains.