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Efficient mucosal vaccination mediated by the neonatal Fc receptor

Nature Biotechnology volume 29, pages 158–163 (2011)Cite this article

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Abstract

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.

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Figure 1: FcRn-targeted mucosal vaccination induces enhanced gD-specific antibody and T-cell responses.
Figure 2: Local immune responses induced by FcRn-targeted mucosal immunization.
Figure 3: FcRn-targeted mucosal immunization provides protective immunity to intravaginal challenge with virulent HSV-2 186.
Figure 4: Increased memory immune response in FcRn-targeted mucosal immunization.

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Acknowledgements

We thank K. Rosenthal and A. Harandi for their discussions of mucosal antigen transport and immunization. We thank G.J. Letchworth for helpful discussions and critical reading of the manuscript. We are grateful to N.E. Simister, Brandeis University, for supplying us with inner medullary collecting duct–FcRn cell line. We acknowledge the receipt of HSV-2 186 strain from L.R. Stanberry, Columbia University, and HSV gD plasmids from P. Spear, Northwestern University. We also acknowledge the helpful discussions with D. Mosser, D. Perez, S. Samal and W. Song. We are most grateful for the technical help from Y. Wang, L. Lu, X. Liu, S. Palaniyandi and Z. Li. This work was supported in part by the National Institutes of Health grants AI65892, AI67965, AI73139 (to X.Z.), DK56597 (to D.C.R.) and MAES competitive grants from the University of Maryland (to X.Z.).

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Authors and Affiliations

  1. Laboratory of Immunology, Virginia-Maryland Regional College of Veterinary Medicine, University of Maryland, College Park, Maryland, USA

    Lilin Ye, Rongyu Zeng, Yu Bai & Xiaoping Zhu

  2. The Jackson Laboratory, Bar Harbor, Maine, USA

    Derry C Roopenian

  3. Maryland Pathogen Research Institute, University of Maryland, College Park, Maryland, USA

    Xiaoping Zhu

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  1. Lilin Ye
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  2. Rongyu Zeng
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Contributions

L.Y. and X.Z. designed and performed experiments, analyzed data and wrote the paper. R.Z. and Y.B. conducted experiments. D.C.R. interpreted data and made editorial suggestions.

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Correspondence to Xiaoping Zhu.

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Ye, L., Zeng, R., Bai, Y. et al. Efficient mucosal vaccination mediated by the neonatal Fc receptor. Nat Biotechnol 29, 158–163 (2011). https://doi.org/10.1038/nbt.1742

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