Phd in IINNOVATION IN IMMUNO-MEDIATED AND HEMATOLOGICAL DISORDERS

Thesis title: UNRAVELING THE MECHANISMS OF B CELL RESPONSE IN HEALTH AND DISEASE ACROSS DIFFERENT AGES: LESSONS FROM THE SARS-COV-2 PANDEMIC

The COVID-19 pandemic was an unprecedented global event because of the extent of disease and mortality caused by the lack of pre-existing immunity to a virus never encountered before. Adaptive immune response can recognize and rapidly eliminate a previously encountered pathogen and to generate long-term memory. Investigation of this part of the immune system led to the rapid development of COVID-19 vaccines and additional interventions able to prevent severe disease and death. However, they were not able to induce sterilizing immunity probably due to the insufficient protection at the site of virus entry and replication, the mucosa of the upper respiratory tract. Children represented a consistent part of the cumulative cases worldwide and also played a significant role in spreading the virus. Although the clinical manifestations in this age group were predominantly mild, severe disease and long-term complications were reported. For this reason, vaccines have been approved and found to be effective also in this age group, but the B cell immune response to vaccination has never been studied. Immunocompromised patients were the main beneficiaries of SARS-CoV-2 vaccines and the evaluation of the mechanisms of immune response to infection and vaccination in people with impaired immunity provided key insights in the advancement of the research in this setting. For these reasons, our work has focused on the extensive study of the mechanisms of B cell immune response to vaccination and infection, focusing on both young and adult, in health and disease conditions. The main objectives of the studies reported below are: 1) To evaluate SARS-CoV-2 vaccine humoral and cellular immunogenicity in healthy children. 2) To describe the durability of memory B cells mediated immunity and the factors regulating the broadening of the B cell immune response in healthy children. 3) To compare MBCs in the peripheral blood with B cells found in nasal and pharyngeal swabs of healthy adults and children, to identify the population closely related to B cells in the mucosal sites able to migrate to the upper airways after SARS-CoV-2 infection and/or vaccination. 4) To investigate the phenotype and function of innate and adaptive lymphocytes in the peripheral blood of adult and pediatric patients splenectomized and born asplenic, to define the specific features of spleen-resident immune cells, and to analyze the role of the spleen in the defense against infection and maintenance of immune memory, by exploring SARS-CoV-2 post splenectomy immunization and infection.