Sialophorin is an essential host element for vaccine immunity against pulmonary fungal infections

Abstract

Abstract The global incidence of fungal infections is alarming due to the increasing immunocompromised population. Vaccine measures are necessary to prevent fungal diseases. Identifying a protective host element as a functional phenotypic marker is immensely valuable as a target to enhance vaccine responses, measure vaccine efficacy, and assess disease outcomes. We identified a host element, O-glycosylated sialophorin, preferentially associated with antifungal memory Tc17 (IL-17A +) cells. Using a mouse model of fungal vaccine immunity during CD4 +T-cell deficiency, we found that sialophorin was essential to bolster vaccine-induced CD8 +T-cell responses and immunity to pulmonary infection. Sialophorin-sufficient CD8 +T cells were superior in responses than the deficient cells under a similar inflammatory micromilieu. Supplementation of sialophorin mAb that binds to O-glycosylated form potentiated the CD8 +T cell responses to fungal antigens, and an inhibitory mAb that binds to non-O-glycosylated form selectively reduced Tc1 (IFNγ +) but not Tc17 cell responses. Sialophorin-mediated immunity was independent of T cell trafficking into the lung. Finally, using fungal antigens vaccination, we show that O-glycosylated sialophorin is a marker of vaccine-potency and immunity. Our study revealed that sialophorin is an essential host element to bolster vaccine responses and serves as a potential biomarker of fungal immunity. NIAID-NIH 5R01AI153522