IgG Serum Antibodies to Shigella sonnei Lipopolysaccharide Are Inversely Associated with the Incidence of Culture-Proven S. sonnei Shigellosis in Israeli Children and Adolescents

Abstract

Background: Shigella is a leading cause of moderate-to-severe diarrhea globally, with young children most affected. The burden of shigellosis drops increasingly with age, inferring the acquisition of natural immunity. We tested the hypothesis that IgG antibodies elicited against Shigella O-specific polysaccharide (O-SP) are correlates of age-acquired immunity. Objectives: We examined levels and determinants of serum IgG to S. sonnei LPS and the association with the incidence of S. sonnei shigellosis in Israeli children and adolescents. Methods: We analyzed 1096 serum samples from 0- to 19-year-olds collected in 2008–2015 for IgG anti-S. sonnei LPS levels by ELISA. Corresponding age-specific incidences of culture-proven S. sonnei shigellosis from 2008 to 2015 were obtained. We compared ecologically IgG levels, prevalence above a proposed protective threshold, and S. sonnei shigellosis incidence. Results: In a multivariable analysis model, children aged 1–4, 5–14, and 15–19 years were 6.71, 27.68, and 48.62 times more likely to have IgG anti-S. sonnei LPS above the threshold than those aged < 1 year, respectively (p < 0.001). Infants 0–3 months old had relatively high IgG anti-S. sonnei LPS levels of maternal origin that dropped thereafter. Children of low socioeconomic status had a 2.73 times higher likelihood of having IgG anti-S. sonnei LPS above the threshold (p < 0.001). A significant inverse correlation between age-specific IgG anti-S. sonnei LPS levels and S. sonnei shigellosis incidence was observed (Spearman rho= −0.76, p = 0.028). Conclusions: The study results support anti-S. sonnei LPS antibodies as correlates of protection that can inform Shigella vaccine development.