Pathobiont driven antibody sialylation through IL-10 undermines vaccination
The pathobiont S. aureus (SA) induces non-protective antibody imprints that underlie ineffective staphylococcal vaccination. However, the mechanism by which SA modify antibody activity is not clear. Herein, we show that IL-10 is the decisive factor that abrogates antibody protection.  SA-induced B10 cells drive antigen-specific vaccine suppression that affects both recalled and de novo developed B cells. Released IL-10 promotes STAT3 binding upstream of sialyltransferase ST3gal4 and increases ST3gal4 expression by B cells, leading to hyper- a2,3 sialylation of antibodies and loss of protective activity. IL-10 enhances a2,3 sialylation on cell-wall associated IsdB, IsdA and MntC antibodies along with suppression of the respective SA vaccines.  Consistent with mouse findings, human anti-SA antibodies as well as anti-pseudomonal antibodies from cystic fibrosis subjects are hyper-sialylated, compared to anti-GAS and pseudomonal antibodies from normal individuals. Overall, we demonstrate a pathobiont-centric mechanism that modulates antibody glycosylation through IL-10 leading to loss of staphylococcal vaccine efficacy. Overall design: Single-cell immune profiling of the S.  aureus IsdB vaccine and aIL-10 treated IsdB vaccine. In this study, we conducted BCR sequencing for three different samples: LAC (LAC-infected mice given adjuvant alone), LAC/IsdB (LAC-infected mice vaccinated with IsdB) and LAC/IsdB/aIL10 (LAC-infected mice vaccinated with IsdB and treated with aIL-10).