110 Broadly neutralizing antibodies for serotherapy and vaccine design.

Memory B lymphocytes and long-lived plasma cells represent a repository of the antigenic experience of an individual. By analyzing the specificity and function of these cells we can gain insights into the human immune response to pathogens and vaccines, identify correlates of protection, and isolate neutralizing antibodies and protective T cells. To interrogate human memory B cell and plasma cell repertoires we developed 2 culture-based high-throughput methods that are used to isolate, with high efficiency, human monoclonal antibodies of distinctive specificities. Unusually potent neutralizing antibodies against human cytomegalovirus were isolated from infected donors and used to identify the viral ligands and to design an experimental vaccine. We also isolated antibodies of exceptional breadth, such as a pan-influenza A neutralizing antibody and an antibody that neutralizes both respiratory syncytial virus and metapneumovirus. By targeting conserved structures, these broadly neutralizing antibodies are less prone to select escape mutants and are therefore promising candidates for prophylaxis and therapy of infections as well as tools for the design of improved subunit vaccines.