VAGINAL MUCOSAL IMMUNITY BASED ON IgG-MUCIN CROSSLINKING

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Creator

Kannan, Arthi
- Affiliation: School of Medicine, Department of Microbiology and Immunology

Abstract

In this thesis, I investigated whether IgG, the predominant antibody in cervicovaginal mucus (CVM), can interact with CVM constituents to protect against Herpes Simplex Virus 1 (HSV-1) infection. Despite the weak affinity between individual IgG molecules and mucins, we hypothesize that multiple virion-bound IgG can avidly crosslink HSV-1 to the mucin mesh, thereby preventing HSV-1 from reaching the target cells. Consistent with this hypothesis, I showed that HSV-1 freely diffused through pH-neutralized CVM with low levels of anti-HSV-1 IgG, but was immobilized in samples with modest levels of endogenous or exogenously added anti-HSV-1 IgG. Removal of the Fc domain and N-glycans from IgG both markedly reduced its trapping potency. Finally, a non-neutralizing monoclonal IgG against HSV-gG provided significant protection against vaginal HSV challenges in mice, and this protection was eliminated in the absence of mucus. These results strongly suggest secreted IgG can work in tandem with mucus to block infections.

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