Shielding the cationic charge of nanoparticle-formulated dermal DNA vaccines is essential for antigen expression and immunogenicity

Joost H. van den Berg, Koen Oosterhuis, Wim E. Hennink, Gerrit Storm, L.J. van der Aa, Johannes F.J. Engbersen, John B.A.G. Haanen, Jos H. Beijnen, Ton N. Schumacher, Bastiaan Nuijen

Research output: Contribution to journalArticleAcademicpeer-review

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Abstract

Nanoparticle-formulated DNA vaccines hold promise for the design of in vivo vaccination platforms that target defined cell types in human skin. A variety of DNA formulations, mainly based on cationic liposomes or polymers, has been investigated to improve transfection efficiency in in vitro assays. Here we demonstrate that formulation of DNA into both liposomal and polymeric cationic nanoparticles completely blocks vaccination-induced antigen expression in mice and ex vivo human skin. Furthermore, this detrimental effect of cationic nanoparticle formulation is associated with an essentially complete block in vaccine immunogenicity. The blocking of DNA vaccine activity may be explained by immobilization of the nanoparticles in the extracellular matrix, caused by electrostatic interactions of the cationic nanoparticles with negatively charged extracellular matrix components. Shielding the surface charge of the nanoparticles by PEGylation improves in vivo antigen expression more than 55 fold. Furthermore, this shielding of cationic surface charge results in antigen-specific T cell responses that are similar as those induced by naked DNA for the two lipo- and polyplex DNA carrier systems. These observations suggest that charge shielding forms a generally applicable strategy for the development of dermally applied vaccine formulations. Furthermore, the nanoparticle formulations developed here form an attractive platform for the design of targeted nanoparticle formulations that can be utilized for in vivo transfection of defined cell types
Original languageEnglish
Pages (from-to)234-240
JournalJournal of controlled release
Volume141
Issue number2
DOIs
Publication statusPublished - 2010

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DNA Vaccines
Nanoparticles
Antigens
Skin
DNA
Extracellular Matrix
Transfection
Vaccination
Static Electricity
Liposomes
Immobilization
Polymers
Vaccines
T-Lymphocytes

Keywords

  • PEGylation
  • Dermal delivery
  • Nanoparticles
  • DNA tattooing
  • DNA vaccination

Cite this

van den Berg, Joost H. ; Oosterhuis, Koen ; Hennink, Wim E. ; Storm, Gerrit ; van der Aa, L.J. ; Engbersen, Johannes F.J. ; Haanen, John B.A.G. ; Beijnen, Jos H. ; Schumacher, Ton N. ; Nuijen, Bastiaan. / Shielding the cationic charge of nanoparticle-formulated dermal DNA vaccines is essential for antigen expression and immunogenicity. In: Journal of controlled release. 2010 ; Vol. 141, No. 2. pp. 234-240.
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abstract = "Nanoparticle-formulated DNA vaccines hold promise for the design of in vivo vaccination platforms that target defined cell types in human skin. A variety of DNA formulations, mainly based on cationic liposomes or polymers, has been investigated to improve transfection efficiency in in vitro assays. Here we demonstrate that formulation of DNA into both liposomal and polymeric cationic nanoparticles completely blocks vaccination-induced antigen expression in mice and ex vivo human skin. Furthermore, this detrimental effect of cationic nanoparticle formulation is associated with an essentially complete block in vaccine immunogenicity. The blocking of DNA vaccine activity may be explained by immobilization of the nanoparticles in the extracellular matrix, caused by electrostatic interactions of the cationic nanoparticles with negatively charged extracellular matrix components. Shielding the surface charge of the nanoparticles by PEGylation improves in vivo antigen expression more than 55 fold. Furthermore, this shielding of cationic surface charge results in antigen-specific T cell responses that are similar as those induced by naked DNA for the two lipo- and polyplex DNA carrier systems. These observations suggest that charge shielding forms a generally applicable strategy for the development of dermally applied vaccine formulations. Furthermore, the nanoparticle formulations developed here form an attractive platform for the design of targeted nanoparticle formulations that can be utilized for in vivo transfection of defined cell types",
keywords = "PEGylation, Dermal delivery, Nanoparticles, DNA tattooing, DNA vaccination",
author = "{van den Berg}, {Joost H.} and Koen Oosterhuis and Hennink, {Wim E.} and Gerrit Storm and {van der Aa}, L.J. and Engbersen, {Johannes F.J.} and Haanen, {John B.A.G.} and Beijnen, {Jos H.} and Schumacher, {Ton N.} and Bastiaan Nuijen",
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van den Berg, JH, Oosterhuis, K, Hennink, WE, Storm, G, van der Aa, LJ, Engbersen, JFJ, Haanen, JBAG, Beijnen, JH, Schumacher, TN & Nuijen, B 2010, 'Shielding the cationic charge of nanoparticle-formulated dermal DNA vaccines is essential for antigen expression and immunogenicity' Journal of controlled release, vol. 141, no. 2, pp. 234-240. https://doi.org/10.1016/j.jconrel.2009.09.005

Shielding the cationic charge of nanoparticle-formulated dermal DNA vaccines is essential for antigen expression and immunogenicity. / van den Berg, Joost H.; Oosterhuis, Koen; Hennink, Wim E.; Storm, Gerrit; van der Aa, L.J.; Engbersen, Johannes F.J.; Haanen, John B.A.G.; Beijnen, Jos H.; Schumacher, Ton N.; Nuijen, Bastiaan.

In: Journal of controlled release, Vol. 141, No. 2, 2010, p. 234-240.

Research output: Contribution to journalArticleAcademicpeer-review

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AU - van den Berg, Joost H.

AU - Oosterhuis, Koen

AU - Hennink, Wim E.

AU - Storm, Gerrit

AU - van der Aa, L.J.

AU - Engbersen, Johannes F.J.

AU - Haanen, John B.A.G.

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AU - Nuijen, Bastiaan

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AB - Nanoparticle-formulated DNA vaccines hold promise for the design of in vivo vaccination platforms that target defined cell types in human skin. A variety of DNA formulations, mainly based on cationic liposomes or polymers, has been investigated to improve transfection efficiency in in vitro assays. Here we demonstrate that formulation of DNA into both liposomal and polymeric cationic nanoparticles completely blocks vaccination-induced antigen expression in mice and ex vivo human skin. Furthermore, this detrimental effect of cationic nanoparticle formulation is associated with an essentially complete block in vaccine immunogenicity. The blocking of DNA vaccine activity may be explained by immobilization of the nanoparticles in the extracellular matrix, caused by electrostatic interactions of the cationic nanoparticles with negatively charged extracellular matrix components. Shielding the surface charge of the nanoparticles by PEGylation improves in vivo antigen expression more than 55 fold. Furthermore, this shielding of cationic surface charge results in antigen-specific T cell responses that are similar as those induced by naked DNA for the two lipo- and polyplex DNA carrier systems. These observations suggest that charge shielding forms a generally applicable strategy for the development of dermally applied vaccine formulations. Furthermore, the nanoparticle formulations developed here form an attractive platform for the design of targeted nanoparticle formulations that can be utilized for in vivo transfection of defined cell types

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JO - Journal of controlled release

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