UC Santa Cruz

Human astrovirus is an important cause of viral gastroenteritis worldwide. Young children, the elderly, and the immunocompromised are especially at risk. Few studies have been conducted examining human astrovirus incidence and seroprevalence to properly assess disease burden and significance. Furthermore, no vaccines or antiviral therapies exist to address human astrovirus infection, but several lines of evidence suggest that a protective antibody response mounted against a childhood infection can prevent future reinfection in adulthood. Therefore, we expect that vaccines eliciting such an antibody response will protect vulnerable individuals from disease. However, successful design of vaccine antigens requires knowledge of how neutralizing antibodies target sites of importance. In this thesis, I discuss my work on the antigenicity and conformational epitopes of the human astrovirus capsid. I begin with our seroprevalence evaluation of all eight classical human astrovirus serotypes in the United States, followed by a review of our simplified workflow for monoclonal antibody sequencing. Finally, I present a structural and mechanistic characterization of two neutralizing monoclonal antibodies which target the human astrovirus capsid spike at two separate, non-overlapping epitopes and both block virus attachment to host cells. These studies provide a basis for the development of therapies to prevent and treat human astrovirus disease.