Advancing the development of tools to better understand humoral responses to sapovirus following natural infections

About This Grant

ABSTRACT Sapovirus (SaV), a genus in the Caliciviridae family alongside norovirus, is increasingly recognized as an important cause of acute gastroenteritis (AGE) in childhood. SaV ranked second among all enteric pathogens in its contribution to AGE incidence in children under 24 months of age in a large multi-site birth cohort study. While vaccines against rotavirus have lowered the burden of childhood AGE and a pediatric norovirus vaccine is in Phase III trials, currently, there are no vaccines against SaV. A major challenge to SaV vaccine development is that there is little known about natural immunity to serve as a guide for vaccine-elicited immunity, including what levels and types of antibodies (Abs) protect against infection. This may be due to the fact that human SaVs are not readily grown in cell culture, hindering infectivity studies and antigen production. Dr. Nordgren at Linköping University has recently implemented SaV cultivation in his lab and has provided as proof of concept that convalescent sera can protect against SaV infection. Our team is uniquely poised to substantially advance the understanding of natural neutralizing immunity to sapovirus with our biobank from field epidemiology research in Nicaragua and state-of-the-art laboratory techniques to measure neutralizing Abs. Leveraging an NIH-funded birth cohort of 444 children in León, Nicaragua, this project aims to characterize the kinetics of neutralizing Abs to SaV in longitudinal serum and stool samples collected from 50 children experiencing a SaV gastroenteritis episode during the first two years of life. In addition, we will test whether polyclonal sera neutralize homotypic and heterotypic SaV, and compare neutralizing Ab levels between children who do and do not develop SaV AGE episodes. We will also determine the correlation between neutralizing Ab levels and levels of IgG and IgA as determined by enzyme immunoassays (EIAs). Together, this unique collaboration and sample set allows us to advance analytic tools to better understand the immunology of sapovirus in children. Most importantly, this project will generate a new tool that will be shared with the scientific community and is fundamental for the understanding of natural humoral immunity to SaV.