Immunological memory confers long term protection against pathogens and is the basis of successful vaccination.
Following antigenic stimulation long lived plasma cells and memory B cells are maintained for a lifetime,
conferring immediate protection and enhanced responsiveness to the eliciting antigen. However, in the case of
variable pathogens such as influenza virus, B cell memory is only partially effective, depending on the extent of
similarity between the preceding and the new viruses. The B cell response is dominated by serotype-specific
antibodies and heterosubtypic antibodies capable of neutralizing several serotypes appear to be extremely rare.
Understanding the basis of broadly neutralizing antibody responses is a critical aspect for the development
of more effective vaccines. In this project we will explore the specificity and dynamics of human antibody
responses to influenza virus by using newly developed technological platforms to culture human B cells and plasma
cells and to analyze the repertoire of human naïve and memory T cells. High throughput functional screenings,
structural analysis and testing in animal models will provide a thorough characterization of the human immune
response. The B cell and T cell analysis aims at understanding fundamental aspects of the immune response such
as: the selection and diversification of memory B cells; the individual variability of the antibody response, the
mechanisms of T-B cooperation and the consequences of the original antigenic sin and of aging on the immune
response. This analysis will be complemented by a translational approach whereby broadly neutralizing human
monoclonal antibodies will be developed and used: i) for passive vaccination against highly variable viruses; ii) for
vaccine design through the identification and production of recombinant antigens to be used as effective vaccines;
and iii) for active vaccination in order to facilitate T cell priming and jump start the immune responses.