The Covid-19 pandemic has shown the massive impact that life threatening pathogens and infectious diseases have on life as we know it. Besides the viral infections that have plagued the world the last years, bacterial infections represent a continuous threat, with bacterial arms becoming more and more resistant against the armoury that we have at our disposal: antibiotics. With ever developing resistance against antibiotics and the rise of multi-drug resistant bacteria new ways for therapeutic intervention have to be brought forward. The ongoing pandemic has also shown the power of vaccination in fighting infectious diseases and indeed vaccination against viral and bacterial infections has been one of the great medical successes. However, many bacterial infections remain that cannot yet be prevented by vaccination. The goal of the PAVax program was to train young scientists in the development of glycoconjugate vaccines, targeting two bacteria that are on the WHO-list of most acute antibiotic-resistant bacteria: Pseudomonas aeruginosa and Staphylococcus aureus. These two bacteria cause life threatening infections, especially in a hospital setting, where they are often found side-by-side in poly bacterial infections. The program has aimed to generate novel vaccine entities, building on the use of polysaccharides found on the exterior of the bacteria, that can be targeted by our immune system. P. aeruginosa and S. aureus express unique glycans that they use to colonize the host and build up a protective biofilm in which they hide from the host immune system. PAVax has aimed to use of these glycans to train our immune system to recognize these glycans and mount an effective immune response. Because it has been shown that glycans by themselves are only weakly immunologically active, they have to be connected to a so-called carrier protein to generate a conjugate vaccine. PAVax has generated ‘designer’ carrier proteins that in combination with P. aeruginosa and S. aureus glycans can elicit a powerful immune response. The glycans that are to be used are isolated from the bacteria, but because this represents a great challenge, organic synthesis has been called upon to deliver the target glycans. This has led to the development of innovative chemistry to assemble the target bacterial glycans of unprecedented complexity and length and the first demonstration that these glycans can be used in anti-Stapylococcal vaccines. The PAVax program has trained four PhD students in a multi-sectorial environment and multidisciplinary program and by performing research in both industry and academia, they have been trained in state-of-the-art of bacterial vaccine development.
