"Hepatitis B virus (HBV), an hepatotropic non-cytopathic DNA virus, still represents a global health problem, with million of deaths for year because of complication of chronic infection. Chronic infection and its outcome are believed a consequence of defective antiviral response, mainly in T-cell arm, probably mediated by prolonged exposition to large amounts of viral antigens. Recently, many advancements have been done on virus-specific CD8 dysfunction or “exhaustion”, while far less is known about the role of other components of immune response. Thus, aims of the present proposal are the evaluation of phenotype and function of CD4 T cells and B cells in both acute self-limited HBV infection, and in chronic HBV, in order to identify correlates of protection, and additional markers of immune impairment. The project will focus on multiple immunological parameters: dynamics of CD4 memory development, and lineage differentiation, B cells memory development and antibodies functional assays, in acute self limited infection; degree and role, if any, of CD4 T and B cells exhaustion in chronic infection, with different degree of viral control. The analysis will be conducted on cryopreserved PBMCs samples of patients affected by HBV (acute or chronic) and will be performed by both molecular and cellular approaches. Interestingly, many of them have been developed at the host institution. Thus, in addition to the possibility to develop a challenging project of strong impact, due to training that the host will provide, the permanence at the host institution, where multiple competences of very high scientific level coexist, will represent for the applicant an unique experience for scientific and working career."