Antigenic Characterization of a Novel Recombinant GII.P16-GII.4 Sydney Norovirus Strain With Minor Sequence Variation Leading to Antibody Escape

Background. Human noroviruses are the leading cause of acute gastroenteritis. Strains of the GII. 4 genotype cause pandemic waves associated with viral evolution and subsequent antigenic drift and ligand-binding modulation. In November 2015, a novel GII. 4 Sydney recombinant variant (GII.P16-GII.4 Sydney) emerged and replaced GII.Pe-GII.4 Sydney as the predominant cause of acute gastroenteritis in the 2016-2017 season in the United States. Methods. Virus-like particles of GII. 4 2012 and GII. 4 2015 were compared for ligand binding and antibody reactivity, using a surrogate neutralization assay. Results. Residue changes in the capsid between GII.4 2012 and GII.4 2015 decreased the potency of human polyclonal sera and monoclonal antibodies. A change in epitope A resulted in the complete loss of reactivity of a class of blockade antibodies and reduced levels of a second antibody class. Epitope D changes modulated monoclonal antibody potency and ligand-binding patterns. Conclusions. Substitutions in blockade antibody epitopes between GII.4 2012 and GII.4 2015 influenced antigenicity and ligand-binding properties. Although the impact of polymerases on fitness remains uncertain, antigenic variation resulting in decreased potency of antibodies to epitope A, coupled with altered ligand binding, likely contributed significantly to the spread of GII.4 2015 and its replacement of GII.4 2012 as the predominant norovirus outbreak strain.