Summary

Summary of the Project

Scientific progress has always been the major driving force for the development of effective vaccines. The first golden age of vaccines started when Pasteur, Koch, Ramon, and Mérieux established the germ theory and developed vaccines based on live‐attenuated or inactivated pathogens and inactivated toxins. A second golden age in vaccine development was a consequence of innovation in cloning and cell culture technologies in the second half of the 20th century allowing the release of protein recombinant vaccines such as vaccines against the hepatitis B, pertussis or papilloma virus. The following implementation of glyco-conjugation chemistry allowed very effective vaccines such as those available against Haemophilus influenzae, pneumococcus, and the meningococcus types A, C, W, and Y. In the last decade, progress in genomics has strongly contributed to vaccine development. The rational selection of candidate antigens based on genomic information, called ‘reverse vaccinology’ allowed the discovery of three protective antigens resulting in the first universal vaccine against type B meningococcus. Despite these major achievements, vaccine generation or improvement for diseases such as HIV, tuberculosis, malaria, dengue, and influenza still represents a global health challenge. These “big five” claim a toll of ~3.5 million deaths per year. Mycobacterium tuberculosis alone infects over one fourth of the human population and causes over 1 million deaths per year. A new wave of technologies in the fields of human immunology and structural biology provides the molecular information will allow the discovery and design of vaccines against pathogens that have been impossible thus far. In this context, the aim of VADEMA is to develop mass spectrometry tools to dissect the immune response following infection or vaccination and to assess the structure of vaccine candidates in their native state and how patient-derived antibodies bind to these.  Taken together, such information will guide selection and optimization of vaccine candidates, promoting antigen design at molecular level with the objective of focusing the immune response toward highly protective epitopes.

R. Rappuoli, A. Santoni and A. Mantovani, (Rappuoli R, et al., 2018), three reference scientists in the fields of vaccinology and immunology, consider vaccination as an achievement of civilization, a human right, our health insurance for the future. To cite the authors: “in the developed world, life expectancy has increased from an average of 40 yr to over 80 yr, and remarkable progress has been made in the developing world as well. Vaccines have played a major role in this dramatic improvement, which is unprecedented in the history of human-kind. Vaccines are the most effective health intervention, and it has been estimated that they will save ~25 million deaths over 10 yr from 2010 to 2020, which is equivalent to five lives saved per minute. In terms of cost-effectiveness, it is estimated that $1 invested in vaccination results in a $10–44 healthcare saving”.

Objectives
Recent technological advances in human immunology and structural biology have provided new reagents and improved tools that allow a better understanding of the basic biological and molecular mechanisms leading to a protective human immune response to pathogens, inspiring new strategies for vaccine design. In this context, VADEMA proposes to combine the characterization of the epitope repertoires recognized during the immune response to pathogens and antigen structure through structural mass spectrometry, with the ultimate goal to provide the rationale for the design of new and more efficacious vaccines against infectious diseases.