Role of CFTR and its downstream signaling in lung barrier failure in pneumonia (Kübler / Suttorp / Witzenrath)
Efficacious vaccines against bacterial pneumonia are sorely needed, and capsular carbohydrates represent attractive vaccine antigens.
Here we will combine our automated carbohydrate synthesis approach with additional innovations to design novel, highly efficient glyco-conjugate vaccines. We will
I. utilize pneumolysin mutants and conserved pneumococcal surface proteins as alternative carbohydrate carriers for synthetic glycotopes.
II. Create fully synthetic glycoconjugates by exploring the use of 5-OP-RU, a conserved small-molecular neoantigen of semi-invariant T cells, called MAIT cells, as carrier for synthetic glycotopes.
III. Perform proof-of-principle vaccine studies in relevant host species, namely pigs.