In addition to polyreactive “natural antibodies” that act as the first line of defense against invading pathogens, “humoral memory” is composed of high affinity antibodies that mediate long-lived immunity against infectious agents, e.g., providing protection against re-infection. The molecular dissection of anti-pathogen B-cell responses using modern technologies to generate specific monoclonal antibodies allowed breakthrough discoveries on antiviral responses to Influenza and HIV. The goal of this proposal is to study memory B-cell antibody responses to human pathogens, especially viruses, by generating and characterizing envelope specific antibodies from infected patients. I propose three aims to address what I believe to be some of the most exciting questions in the field of antiviral B-cell immunity. I propose to study: (i) the development and dynamics of memory B-cell responses to HIV; (ii) the mucosal antibody response to HIV; (iii) the memory B-cell response to Chikungunya virus. The antibodies that will be produced may be of therapeutic interest, but more importantly, their characterization will lead to a better understanding of human antibody responses to infectious agents, and may uncover candidate immunogens for vaccine development.