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A training network for the rational design of the next generation of well-defined glycoconjugate vaccines

Periodic Reporting for period 2 - GLYCOVAX (A training network for the rational design of the next generation of well-defined glycoconjugate vaccines)

Reporting period: 2017-11-01 to 2019-10-31

GLYCOVAX is a network for the education of promising young scientists to the rational design of well-defined and innovative glycoconjugate vaccines to improve current therapies and tackle unmet medical needs. Vaccination with carbohydrate-protein conjugates have made possible to save millions of lives, by preventing meningitis, pneumoniae and other life threating diseases. Due to the increase of antibiotic resistance, it is expected that in the next years vaccination will be applied to tackle unmet medical needs, and for prevention of microbial infections caused by antibiotic resistant microorganisms, pandemic infections, and diseases for travelers to areas afflicted by diseases no longer present in the country of origin. Vaccination can aid reducing the use of broad-spectrum antibiotics since it can provide protection (herd immunity) also for individuals who are not vaccinated.
The quality and immunological activity of future glycoconjugate can be improved by merging the most advanced techniques for selection of the carbohydrate to be linked to the protein, fast production of these carbohydrates and connection at specific sites of the protein.
The science developed under the GLYCOVAX programme has been applied to improve existing vaccines (as in the case of Neisseria meningitidis) and to epidemiologically relevant disease areas for which no therapy is yet available: neonatal infections (Group B Streptococci, GBS), and nosocomial infections (Enterococci, Staphylococcus aureus).
To achieve its scope, GLYCOVAX was organized into four scientific work-packages, covering methods for carbohydrate preparation, including the innovative carbohydrate automated synthesis, carbohydrate-protein interaction studies, strategies for site-selective protein conjugation and screening of the produced glycoconjugate vaccine candidates.
A unique feature of GLYCOVAX has been the profound interaction between academic and industry, which resulted from a network composed of eight academic groups, one industrial partner and one small medium size enterprises (SMEs). An additional SME complemented the GLYCOVAX consortium for the administrative management and organizing training course. The partners have offered expertise in carbohydrate chemical/enzymatic synthesis, conjugation techniques, high throughput screening technology, structural glycobiology, vaccinology and immunology, and project management. In total, 14 Early Stage Researchers (ESR) have worked on the four ambitious work packages and have been exposed to the most innovative ideas and techniques in the growing field of glycoscience and vaccinology. They have been trained by an intensive program of workshops, summer schools, seminars, and secondments; finally, the training has been complemented with transferable skills courses.
The multi-disciplinary approach of the GLYCOVAX network has substantially increased the knowledge on glycoconjugate vaccines, enabling a better understanding of the features impacting on the immunogenicity of conjugates under clinical development (e.g. GBS). Furthermore the network has generated new methodologies for pathogen-free production of antigens and new approaches for linking carbohydrates to proteins leading to vaccines with high quality standards and improved characteristics. Importantly, the network has also contributed to identify new potential vaccine candidates for disease against which no preventive therapy is currently available (e.g. antimicrobial resistant Enterococci). Overall these achievements have allowed advancing the field of glycoconjugate towards rational design.
The dissemination and outreach of the project activities targeted a broad range of stakeholders, from scientific parties to wider public audiences, thus resulting in a high visibility and impact of the project outcome.
"GLYCOVAX has delivered building blocks and strategies (liquid phase and solid phase automated syntheses, chemoenzymatic synthesis and other synthetic approaches) for the synthesis of surface bacterial glycans from a variety of pathogens, including N. meningitis, Group B Streptococcus and Enterococci. Functional monoclonal antibodies specific for the natural polysaccharides from these pathogens have been also produced and used to map by modern physico-chemical techniques immunologically relevant portions of these carbohydrates and to select in vitro selection of the most promising synthetic glycan to be tested as vaccine candidates.
All the students involved in GLYCOVAX have attended six network workshops, where they have received lectures from internal and external experts in the field, and three transferable skills courses.
Nine articles have been published and novel IP has been generated in the field of meningitis and streptococcal pathogens.
Students have been involved in dissemination and public engagement activities both at international and local level. GLYCOVAX aims and results have been spread through communications and posts on social media (e.g. Twitter #glycovax) and GLYCOVAX website, (https://www.glycovax.eu/) which also includes a video shot by the ESRs, where all the fellows, with seven different nationalities, illustrate GLYCOVAX aims each of them in his own language."
The integrated scientific approach used in GLYCOVAX has allowed to develop a rational approach for vaccine design leading to glycoconjugate vaccines with higher quality control standards, with no need to use the pathogen as carbohydrate source and characteristics optimized in order to maximize the immunological activity. We expect that this will impact the current process of vaccine manufacturing making it safer, more robust and controllable. Results have led to a patent application and eight publications.
Most importantly, the advancement of these technologies has allowed identifying novel vaccines to combat diseases for which there is no preventive therapy available (e.g. Enterococci). This could potentially have a strong impact in terms of improved public healthcare standards, reduction of costs compared to current medical treatments, and minimization of the use of antibiotics.
Training in both scientific and transferable skills already received by the young scientists during GLYCOVAX have strengthened their technical and soft skills. The courses, together with training already ongoing at the partner premises, have guaranteed that all the students received top quality scientific knowledge and were exposed to various complementary topics to foster their entrepreneurial mind-set. The intersectoriality and interdisciplinary aspect of the partnership has created a strong collaborative environment that will continue beyond GLYCOVAX and has educated young scientists ready to the challenges of global technology and with open and network oriented mindset.
This project has received funding from the European Union's Horizon 2020 research and innovation programme under grant agreement No 675671.