Periodic Reporting for period 2 - VADEMA (Doctoral Industrial School for Vaccine Design through Structural Mass Spectrometry)
Reporting period: 2018-11-01 to 2020-10-31
To cite Rappuoli, Santoni and Mantovani, (Rappuoli R, et al., 2018), three reference scientists in the fields of vaccinology and immunology, “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.”
Recent technological advances in human immunology and structural biology have provided new reagents and improved tools to 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 proposed 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.
The grant was centred on two topics, the first one focused on gaining conformational information of antigens in native state (i.e. those are present in the bacterial outer membrane) and the second one deals with dissecting the humoral response following infection or vaccination.
Conformational information of antigen in native state: The scientific and technological goals so far reached include the construction of a combination of a strong transcription promoter with an adequate chaperone to express and localize membrane antigens in outer membrane vesicles; the definition of a tag to enrich low expressed proteins compatible with the structural mass spectrometry protocol, and the set-up of a new protocol to separate lipids and proteins to enable mass spectrometry analysis. This last approach allowed to evidence conformational difference of antigens in their native (membrane -associated) and recombinant forms.
Dissecting the humoral response following infection or vaccination: The basis for a new protocol for epitope mapping of a polyclonal population has been put in place using sera from immunized animals. This new protocol has been applied with success to identify immuno-dominant epitope in human vaccines. Moreover, new method for de novo sequencing of IgG purified from vaccinated subjects is currently under development.
Training: The fellows are affiliated to the Drug Research Academy where they benefited from interactions with a wide and diverse scientific network within the academic and industrial pharmaceutical research community. The fellows are attending courses foreseen at the Graduate School in Copenhagen which make up the main curriculum for their Ph.D. Complementary courses on mass spectrometry and vaccinology will also be held during the fellowship. The fellows could participate to numerous seminars provided by worldly recognized scientists either by the University of Copenhagen or GSK Vaccines.
Transferable skills: At the same time, the students acquired transferable skills e.g. in scientific communication and presentation of scientific data, project management and intellectual property as well as fund raising and entrepreneurship which will equip them to become future leaders of academic or industrial research.