Efficient mucosal vaccination mediated by the neonatal Fc receptor.
Almost all infectious diseases are initiated at mucosal surfaces, yet intramuscular or subcutaneous vaccination usually provides only minimal protection at sites of infection owing to suboptimal activation of the mucosal immune system. The neonatal Fc receptor (FcRn) mediates the transport of IgG across polarized epithelial cells lining mucosal surfaces. We mimicked this process by fusing a model antigen, herpes simplex virus type-2 (HSV-2) glycoprotein gD, to an IgG Fc fragment. Intranasal immunization, together with the adjuvant CpG, completely protected wild-type, but not FcRn knockout, mice after intravaginal challenge with virulent HSV-2 186. This immunization strategy induced efficient mucosal and systemic antibody, B- and T-cell immune responses, with stable protection for at least 6 months after vaccination in most of the immunized animals. The FcRn-IgG transcellular transport pathway may provide a general delivery route for subunit vaccines against many mucosal pathogens.
Laboratory of Immunology, Virginia-Maryland Regional College of Veterinary Medicine, University of Maryland, College Park, Maryland, USA.
Lilin
L
Ye
Rongyu
R
Zeng
Yu
Y
Bai
Derry C
DC
Roopenian
Xiaoping
X
Zhu
D058956:Administration, Mucosal; D000818:Animals; D002460:Cell Line; D016207:Cytokines / Q000378:metabolism; D005260:Female; D005434:Flow Cytometry; D015395:Histocompatibility Antigens Class I / Q000235:genetics / Q000276:immunology / Q000378:metabolism*; D007074:Immunoglobulin G / Q000235:genetics / Q000276:immunology / Q000378:metabolism; D053208:Kaplan-Meier Estimate; D051379:Mice; D018345:Mice, Knockout; D058990:Molecular Targeted Therapy / Q000379:methods; D009092:Mucous Membrane / Q000276:immunology / Q000378:metabolism*; D011961:Receptors, Fc / Q000235:genetics / Q000276:immunology / Q000378:metabolism*; D011993:Recombinant Fusion Proteins / Q000235:genetics / Q000276:immunology / Q000378:metabolism; D014612:Vaccines / Q000008:administration & dosage* / Q000276:immunology / Q000493:pharmacokinetics*; D014621:Vagina / Q000276:immunology; D014759:Viral Envelope Proteins / Q000235:genetics / Q000276:immunology / Q000378:metabolism
D016207:Cytokines; D015395:Histocompatibility Antigens Class I; D007074:Immunoglobulin G; D011961:Receptors, Fc; D011993:Recombinant Fusion Proteins; D014612:Vaccines; D014759:Viral Envelope Proteins; C040570:glycoprotein D-herpes simplex virus type 2; C100688:Fc receptor, neonatal
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