Work | research

Work

In this section you can read about the highlights of previous and current research as well as a summary of the relevant findings.

Universal Influenza Vaccine

By using iQur's Tandem Core Virus-Like Particle (VLP) , we were able to combine a total of 5 universal influenza (A) antigens derived from the HA-stalk and Matrix protein 2. Vaccination with our universal vaccine candidate produces cross-reactive antibody to Hemagglutinin from every clade and subtype. Pre-clinical data shows excellent protection profiles against all H1N1 and H3N2 strains tested thus far. More info here and here.

In ongoing work we are optimising large scale GMP production for a human phase 1 trial.

Functional Inflammasome Responses in the Aged

We were able to determine that following stimulation with a TLR4 agonist (LPS) macrophages from aged mice produce a lower amount of pro-IL1β intra-cellularly. Accordingly this translates into a lower amount of secreted IL-1β when the inflammasome is engaged by ATP. However, we found out that if Caspase-1 is activated by ATP when BMM from both young and aged mice have a comparable intra-cellular content of pro-IL-1β, then the secreted contents of IL-1β are also comparable. The same is true for IL-18. This demonstrates that the inflammasome pathway itself works with a similar efficiency in BMM from aged mice. Therefore the observed deficiencies in IL-1β production in macrophages from aged mice using the LPS+ATP system are due to some component downstream of TLR4 signalling and not likely due to NLRP3 dysfunction. More details can be found here.

LT(K)63 Protects from Lethal Influenza Infection

LT(K)63, or LTK63, is a bacterial E.coli derived molecule from the CT and LT family of toxins. LTK63 was developed by Novartis as a potential mucosal adjuvant, which carries all the immunological characteristics of LT and LTB but without any of the toxicity. The single aa change (K-lysine) at locus 63 within the active site renders the molecule enzymatically inactive. We discovered that a single i.n. dose of LTK63 delivered 6-8 days before infection can protect the highly susceptible DBA-1 mouse from a lethal influenza (H3N2) infection. The protection is associated with decreased weight loss, lower lung neutrophilia and improved viral clearance. Protection is conferred only during a narrow window, where mice fail to be protected if LTK is administered less than 5 days or over 21 days prior to the infection. This transient protective window coincides with elevated CD4+ and CD8+ T-cells in the lung and alveolar space.