High Serum Levels of Norovirus Genotype-Specific Blocking Antibodies Correlate With Protection From Infection in Children

Background. Norovirus is a common cause of acute gastroenteritis in children. Serum immunoglobulin G (IgG) antibodies have been implicated in protection against norovirus-associated gastroenteritis, but the level, specificity, and functionality necessary for protection remain to be elucidated. Methods. Norovirus-specific IgG antibodies to genogroup II (GII)-4-2010 New Orleans (NO), GII-4-1999, GII-12-1998, GI-1-2001, and GI-3-2002 virus-like particles (VLPs) were determined by enzyme-linked immunosorbent assay in serum samples collected from children who presented to the hospital because of acute norovirus gastroenteritis in 2009-2011. The blocking activity of the antibodies was tested in a surrogate neutralization assay. Results. Most norovirus infections (62.8%) in the study population were caused by a GII-4 NO variant. Children who acquired GII-4 NO infection had a low preexisting type-specific IgG level and blocking activity of the sera, in contrast to children infected with other Gil genotypes. Following GII-4 NO infection, genotype-specific seroconversion and a corresponding increase in blocking antibody potential was observed. Although seroconversion to the heterologous GII-4-1999 variant was observed, there was no corresponding increase in the specific blocking antibody titer. There was no concomitant seroconversion against GI VLPs, indicating a highly genogroup-specific antibody response. Conclusions. High preexisting norovirus genotype-specific serum IgG titers and blocking activity in children indicate protection from norovirus infection in a strain-specific manner.