A training network for the design of new synthetic carbohydrate-based vaccines to combat antibiotic resistant Pseudomonas aeruginosa

Projektbeschreibung

Synthetische Impfstoffe gegen antibiotikaresistentes Pseudomonas aeruginosa

Pseudomonas aeruginosa ist ein gramnegatives krankheitserregendes Stäbchenbakterium. Dieses multiresistente Pathogen besitzt komplexe Widerstandsmechanismen gegen Antibiotika, bildet Biofilme aus und wird mit Krankenhausinfektionen wie beatmungsinduzierter Lungenentzündung oder Sepsis in Verbindung gebracht. Die Biofilmmatrix von Pseudomonas aeruginosa besteht aus Alginat und den zwei essenziellen Zuckern (Exopolysacchariden) PSL und PEL. Das EU-finanzierte Projekt PAVax wird diese Saccharide erforschen und nutzen, um daraus neuartige zielgerichtete Impfstoffe zu entwickeln. Um seine ehrgeizigen Ziele zu erreichen, vereint das Konsortium die komplementäre Expertise seiner Partner aus Wissenschaft und Industrie. Dank der gemeinsamen Anstrengungen und Zusammenarbeit der Partner erhalten die vier Nachwuchsforschenden im Projekt eine professionelle Ausbildung auf höchstem Niveau.

Ziel

PAVax is a network that will train 4 early-stage researchers (ESRs) on the conception of new synthetic vaccines to combat the antibiotic resistant bacterium Pseudomionas aeruginosa (PA), for which there currently is no adequate vaccine available. This consortium will explore and exploit the use of PA-exopolysaccharides that play a key role in biofilm formation that protects the bacterium from its environment: alginate, Psl and Pel. We will exploit these saccharides to generate novel vaccines targeting these exposed polysaccharides. Next to the isolation of these polysaccharides from the bacteria, we will employ synthetic chemistry to deliver well-defined fragments of these polysaccharides. These will be used to map the interactions of the saccharides with antibodies to inform on the structure of the optimal epitope. We will conjugate the (synthetic) fragments to newly discovered PA proteins to generate conjugate vaccines targeting multiple PA entities. The consortium is formed by an academic partner, Leiden University (NL) and an industrial partner, GSK Vaccines, Siena (IT), harnessing the complementary expertise of both partners to achieve the ambitious goals set. The close collaboration between the two partners will ensure training of the ESRs at the highest level and best synergy possible. The ESRs will receive intersectorial, international and interdisciplinary training in (synthetic) carbohydrate chemistry, vaccine design, protein chemistry and conjugation, biophysical interaction studies, and immunology. With the ever-growing awareness of the importance of carbohydrates in health and disease, and the continuous threat of multidrug resistant bacteria, the skill set acquired by the ESRs will prepare them to face the major scientific and societal challenges ahead and become important players in academic or industrial research in the future