We are interested in exploring protective immunity against infectious diseases, especially influenza, enteroviral infections, and COVID-19, investigating the interaction between human immunity and antigenic evolution of pathogens, and developing novel antibody-based therapeutic approaches. We build a library of human monoclonal antibodies that recognize emerging and re-emerging pathogens and characterize their antigenic breadth and function in detail. For example, we delineate the breadth and potency of human B cell-derived antibody response to enterovirus A71 (EV-A71) in children with hand, foot, and mouth diseases. We find that neutralizing antibodies that target the rims and floor of viral capsid canyon exhibit broad and potent activities against multi-genotype viruses spanning the years 1998-2019, several inhibit viral infectivity both at pre- and post-attachment stages and prevent severe motor deficit and death in susceptible mice with lethal challenge. Collaborative work with structural biologists is ongoing to establish a comprehensive understanding of neutralizing anti-capsid antibody response at the molecular level. Recently, we are studying human B cell and antibody responses to SARS-CoV-2 in immunized and infected individuals. We identify a subset of neutralizing antibodies that target a new and highly conserved epitope on the spike of SARS-CoV-2, and such an antibody creates a real potential for a synergic antiviral effect in combination with ACE2-blocking antibodies.
