Structural and Mechanistic Studies on an Astrovirus-Neutralizing Antibody: Implications for Vaccine Design and Antiviral Therapies
- Author(s): Bogdanoff, Walter Arturo
- Advisor(s): DuBois, Rebecca M
- et al.
Human astrovirus (HAstV) is a leading cause of viral diarrhea in young children. HAstV is also associated with chronic diarrhea and even systemic infection in immunocompromised patients. Currently, no vaccines or antiviral therapies exist for HAstV infections. Several lines of evidence point to the presence of protective antibodies in healthy adults as a mechanism governing protection against future HAstV infection. Thus, we hypothesize that a vaccine that elicits protective antibodies will protect children from HAstV disease. A fundamental gap in our knowledge is an understanding of the binding sites and mechanisms of action of neutralizing antibodies that block HAstV infection. Our studies demonstrate that a single domain in the HAstV capsid protein is involved in binding to a potent neutralizing antibody. Furthermore, we have exciting structural and mechanistic studies on both the HAstV capsid domain and the neutralizing antibody. The overall studies have uncovered a point of vulnerability on the HAstV virus capsid surface and can lead the way for the development of a safe and effective prophylactic vaccine.