Lisa Lindesmith
University of North Carolina, USA
Title: Norovirus diversity and immune driven evolution: Mechanisms of protection and implications for vaccine design
Biography
Biography: Lisa Lindesmith
Abstract
Noroviruses (NoVs) are the leading cause of human acute gastroenteritis. Strains within the GII.4 genotype drive pandemic levels of infection every 2-3 years. Each pandemic strain correlates with evolution in the major capsid protein and emergence of a GII.4 strain with distinct antigenic and ligand binding properties. GII.4 strain emergence and extensive antigenic heterogeneity among the >40 additional NoV genotypes are primary obstacles to development of an efficacious vaccine. Multivalent virus-like particle (VLP) vaccination shows promise for overcoming these challenges. Volunteers vaccinated simultaneously with GI.1 and GII.4C VLPs generated broad cross-genotype blockade antibody responses, a surrogate measurement for protective immunity. Importantly, breadth of blockade antibody response extended to novel GII.4 VLPs that had not circulated prior to sample collection, indicating that vaccination may provide protection from emergent strains.The breadth and uniformity of the blockade antibody response across antigenically diverse GII.4 strains suggests that immunization primarily activated a memory antibody response to multiple GII.4 strains. Antigenic cartography and epitope-specific blockade-of-binding assays support this finding. These results are in contrast to the observed strain-specific secondary antibody response to the GI.1 vaccine component and identify pre-exposure history, mediated by host genetics, as a key determinant to NoV vaccine response.