Denver Russell Memorial Lecture 2018
14 Nov 2018
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Mariagrazia received her degree in Chemistry and Pharmaceutical Technologies at the University of Naples, Italy. Following a period at the EMBO laboratories in Heidelberg, Germany, she moved to Siena, Italy where she has been ever since leading many bacterial projects. She contributed to the discovery of a pertussis vaccine based on a genetically detoxified toxin, and to the discovery of a new vaccine against Meningococcus B vaccine, licensed in many countries worldwide. Mariagrazia is currently Senior Scientific Director Bacteriology at GSK Vaccines, in Siena. She has received many scientific awards and is elected member of EMBO, of European Academy, European Academy of Microbiology, Fellow of the American Academy of Microbiology and Vice President of IUMS (International Unit of Microbiology Societies). Mariagrazia is also Honorary Visiting Professor at the University of Leicester. She has over 190 publications in international peer-reviewed journals and is co-inventor of many patents.
Vaccines have had a major impact on human health over the past two centuries, allowing for the control and elimination of many infectious diseases. In the last years, important discoveries in the field of chemistry, microbiology and immunology and the development of new and sophisticated technologies have provided alternatives to the design of improved vaccines or of novel vaccines against infections for which preventive measures do not exist.
New generation conjugated vaccines, based on the conjugation of bacterial polysaccharides to proteins have dramatically reduced the incidence of bacterial meningitis. The genome sequencing introduced in the late ‘90s has completely changed the landscape of vaccine antigen discovery. It is now possible to identify antigens starting from the genome of a microorganism. This approach has allowed the identification of three main antigens as basis of a new vaccine against Neisseria meningitidis serogroup B, a bacterium causing a devastating disease characterized by meningitis and sepsis. The three antigens, in combination with OMV from a New Zealand outbreak strain, are the basis of the multicomponent MenB vaccine, licensed for use in infants and adolescents.
By high-throughput cloning of human B cells from subjects immunized with the MenB vaccine, human monoclonal antibodies against each of the three antigens have been isolated and functional epitopes mapped by Protein array, HDX and X-Ray structures. This analysis has provided an interesting outlook in the immunological properties of the menB antigens and on the sequence conservation of the immunogenic regions.
In future, the study of the immunological features of the antigens, of their structure and genetic diversity, are expected to guide the structure-based design of ideal vaccine antigens for new generation vaccines, based on multiple antigens, more stable and more cross-protective.