Systemic IgG responses to glycosylated mucinase YghJ after experimental enterotoxigenic Escherichia coli infection.

Abstract

Background: The availability of a broadly protective vaccine against pathogenic Escherichia coli could help to reduce morbidity and mortality from severe gastrointestinal and systemic infections. E. coli vaccine development efforts often target protein virulence factors that natively are extensively glycosylated, but this glycosylation is absent from recombinantly produced vaccine antigens. Human IgA responses to the conserved virulence factor YghJ have recently been shown to frequently target glycosylated epitopes. Here we evaluated to what extent anti-YghJ IgG responses also target glycosylated epitopes, longevity of these responses, and to what extent the responses correlated with the IgA responses.

Methods: Multiplex bead flow cytometric immunoassays were used to evaluate changes in anti-YghJ IgG levels and glycosylation specificity in serum and antibody in lymphocyte supernatant (ALS) collected from 21 volunteers experimentally infected with enterotoxigenic E. coli (ETEC) strain TW10722.

Results: Following infection, most volunteers had substantially increased anti-YghJ IgG levels both in serum and ALS. The proportion of serum anti-YghJ IgG that specifically targeted glycosylated epitopes increased from 0.10 (Interquartile range [IQR]: 0.07, 0.21) before to 0.17 (IQR: 0.11, 0.38) 10 days after dose ingestion before returning to pre-infection levels after 28 days. The glycosylation-specific proportions correlated between IgG and IgA for both serum and ALS.

Conclusion: Our findings indicate that glycosylated epitopes are an important target for antibody immune responses and may play an important role in host immunity during the early phase of infection.