Infectious Disease
Assessing correlates of protection against norovirus infection and disease Savannah M. Hammerton* Savannah Hammerton W. Zane Billings Ye Shen Amy K. Winter Andreas Handel
Norovirus is a major cause of acute gastroenteritis cases worldwide and in the United States. Despite this, correlates of protection against norovirus infection and disease outcomes are poorly understood, and no vaccines are available. We evaluated the relationships between pre-challenge GI.1 and GII.4 norovirus antibodies and clinical outcomes in two vaccine studies with post-vaccination challenge components. The first study assessed a monovalent GI.1 vaccine, and the second assessed a GI.1 and GII.4 bivalent vaccine. We analyzed histo-blood group antigen (HBGA) blocking titers, serum IgA and IgG, and total antibody ELISA (Pan-Ig). All antibody titers were genotype-specific. The outcomes were protection against PCR-confirmed infection, protection against vomiting or diarrhea any day post-challenge (VorD), protection against protocol-defined illness (PDI), and a modified Vesikari Scoring Scale for disease severity. We used Bayesian logistic regression models to assess antibody relationships with infection, VorD, and PDI, and gamma-poisson models to assess antibody relationships with Vesikari scores. We found differences in relationships between vaccine and placebo groups and inconsistent associations between antibodies and clinical outcomes. Our findings indicate that, currently, humoral CoPs may not reliably indicate protection against norovirus clinical outcomes.