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

PAVax is an innovative, international, intersectorial and interdisciplinary doctoral training network that aims at the education of a new generation of glycoscientists able to provide key findings for the design of new carbohydrate-based vaccines for the prevention of Pseudomonas aeruginosa (PA) and Staphylococcus aureus (SA) infections. Antibiotic resistance of these bacteria seriously thwarts therapeutic intervention of these infections.

The PAVax project combines excellence in carbohydrate chemistry/conjugation and glycoimmunology, deriving from Leiden Universities' expertise in carbohydrate synthesis and process automation and GSK’s background in purification, structural glycobiology, conjugation and immunological characterization of polysaccharides to unite these strengths in the design and conception of the next generation PA/SA-vaccines.

PAVax will create a unique, multidisciplinary and intersectoral training programme that will enable 4 early stage researchers (ESRs) to be trained in the most innovative approaches in the growing field of glycoscience and vaccinology and to simultaneously acquire transferable skills, allowing then to develop into future leaders in academic or industrial research.

Challenge

Antibiotic resistance of PA/SA is a major concern and treatment of infections can be very challenging, since most PA and SA strains are resistant to at least one of the classes of antibiotics, and a few are even resistant to all antibiotics available. WHO/CHO signaled alarming concerns towards a series of antibiotic resistant bacteria, the so called ESKAPE pathogens (ESKAPE is an acronym for Enterococcus feacium, Staphylococcus aureus, Klebsiella pneumonia, Acinetobacter baumannii, Pseudomonas aeruginosa and Enterobacter), including PA and SA. Clearly there is an urgent need for new preventive therapies to be used in replacement or in association with current antiobiotic treatments.

Opportunities

Surface carbohydrates, particularly capsular polysaccharides (CPS), have been proven to be optimal targets for bacterial vaccine development. Because of their T-cell independent character, carbohydrates need to be covalently linked to a carrier protein to provide a vaccine, offering adequate protection in high-risk groups, such as infants and children under 2 years of age. Nowadays glycoconjugate vaccines are used to control a variety of bacterial infections, such as those caused by Haemophilus influenzae, Streptococcus pneumoniae and Neisseria meningitidis, and they are part of vaccination programs worldwide.

Benefits
  • Advancement of a structure-based vaccine design approach using PA and SA as model.
  • Development of new methods for carbohydrate synthesis and glycoconjugation.
  • Education of the next generation of highly motivated, entrepreneurial scientists with intersectorial, multi-disciplinary skills and expertise to advance twenty-first century carbohydrate-based vaccines to combat antibiotic resistant pathogens.
  • Enhanced entrepreneurship, creativity and innovation in vaccine design across Europe.