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A Protective Allergy Vaccine Based on CpG- and Protamine-Containing PLGA Microparticles

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An Erratum to this article was published on 10 July 2007

Abstract

Purpose

Allergen-specific immunotherapy (SIT) requires dozens of subcutaneous injections over 3 to 5 years in order to control IgE-mediated hypersensitivity, which is a T-helper 2 (Th2)-associated pathology. This study investigates the use of poly(lactide-co-glycolide) (PLGA) microparticles combined with immunostimulatory oligodeoxynucleotide (CpG), as well as protamine in SIT.

Materials and Methods

We prepared microparticle formulations with the major allergen of bee venom, phospholipase A2 (PLA2), and analyzed the effect of co-encapsulated or admixed CpG in both naïve and bee venom allergic mice.

Results

Mice immunized with microparticles containing only PLA2 induced weak antibody responses. In contrast, the combination with CpG resulted in strong PLA2-specific antibody responses. The presence of CpG was required for the induction of the Th1-associated isotype IgG2a, and the titers of IgG2a in sensitized mice correlated with a better protection against an allergen challenge. The effect of CpG was further strengthened when protamine was co-encapsulated for complexation of CpG.

Conclusions

This study shows that allergen-specific immunotherapy with a PLGA-based allergen-delivery system in combination with CpG enhanced the induction of protective IgG2a immune responses. This may improve SIT compliance and shorten its duration.

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Acknowledgements

The authors thank Mrs. María J. Pena Rodríguez for help with ELISA measurements, Mrs. Nathalie Schlegel and Dr. Nicole Graf for English editions, and Prof. Adriano Aguzzi for helpful discussions.

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Authors and Affiliations

  1. Unit for Experimental Immunotherapy, Department of Dermatology, University Hospital Zurich, Gloriastrasse 31, 8091, Zurich, Switzerland

    Julia M. Martínez Gómez, Thomas M. Kündig & Pål Johansen

  2. Drug Delivery and Formulation, Institute of Pharmaceutical Sciences, ETH Zurich, Zurich, Switzerland

    Stefan Fischer, Noèmi Csaba, Hans P. Merkle &  Bruno Gander

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  1. Julia M. Martínez Gómez
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Correspondence to Pål Johansen.

Additional information

An erratum to this article can be found at http://dx.doi.org/10.1007/s11095-007-9386-1

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Gómez, J.M.M., Fischer, S., Csaba, N. et al. A Protective Allergy Vaccine Based on CpG- and Protamine-Containing PLGA Microparticles. Pharm Res 24, 1927–1935 (2007). https://doi.org/10.1007/s11095-007-9318-0

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