Synergistic effects of dendritic cell targeting and laser-microporation on enhancing epicutaneous skin vaccination efficacy

Yoan Machado, Sanne Duinkerken, Veronika Hoepflinger, Melissa Mayr, Evgeniia Korotchenko, Almedina Kurtaj, Isabel Pablos, Markus Steiner, Angelika Stoecklinger, Joyce Lübbers, Maximillian Schmid, Uwe Ritter, Sandra Scheiblhofer, Michael Ablinger, Verena Wally, Sarah Hochmann, Anna M. Raninger, Dirk Strunk, Yvette van Kooyk, Josef Thalhamer & 1 others Richard Weiss

Research output: Contribution to journalArticleAcademicpeer-review

Abstract

Due to its unique immunological properties, the skin is an attractive target tissue for allergen-specific immunotherapy. In our current work, we combined a dendritic cell targeting approach with epicutaneous immunization using an ablative fractional laser to generate defined micropores in the upper layers of the skin. By coupling the major birch pollen allergen Bet v 1 to mannan from S. cerevisiae via mild periodate oxidation we generated hypoallergenic Bet-mannan neoglycoconjugates, which efficiently targeted CD14+ dendritic cells and Langerhans cells in human skin explants. Mannan conjugation resulted in sustained release from the skin and retention in secondary lymphoid organs, whereas unconjugated antigen showed fast renal clearance. In a mouse model, Bet-mannan neoglycoconjugates applied via laser-microporated skin synergistically elicited potent humoral and cellular immune responses, superior to intradermal injection. The induced antibody responses displayed IgE-blocking capacity, highlighting the therapeutic potential of the approach. Moreover, application via micropores, but not by intradermal injection, resulted in a mixed TH1/TH17-biased immune response. Our data clearly show that applying mannan-neoglycoconjugates to an organ rich in dendritic cells using laser-microporation is superior to intradermal injection. Due to their low IgE binding capacity and biodegradability, mannan neoglycoconjugates therefore represent an attractive formulation for allergen-specific epicutaneous immunotherapy.

Original languageEnglish
Pages (from-to)87-99
Number of pages13
JournalJournal of Controlled Release
Volume266
DOIs
Publication statusPublished - 28 Nov 2017

Cite this

Machado, Yoan ; Duinkerken, Sanne ; Hoepflinger, Veronika ; Mayr, Melissa ; Korotchenko, Evgeniia ; Kurtaj, Almedina ; Pablos, Isabel ; Steiner, Markus ; Stoecklinger, Angelika ; Lübbers, Joyce ; Schmid, Maximillian ; Ritter, Uwe ; Scheiblhofer, Sandra ; Ablinger, Michael ; Wally, Verena ; Hochmann, Sarah ; Raninger, Anna M. ; Strunk, Dirk ; van Kooyk, Yvette ; Thalhamer, Josef ; Weiss, Richard. / Synergistic effects of dendritic cell targeting and laser-microporation on enhancing epicutaneous skin vaccination efficacy. In: Journal of Controlled Release. 2017 ; Vol. 266. pp. 87-99.
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title = "Synergistic effects of dendritic cell targeting and laser-microporation on enhancing epicutaneous skin vaccination efficacy",
abstract = "Due to its unique immunological properties, the skin is an attractive target tissue for allergen-specific immunotherapy. In our current work, we combined a dendritic cell targeting approach with epicutaneous immunization using an ablative fractional laser to generate defined micropores in the upper layers of the skin. By coupling the major birch pollen allergen Bet v 1 to mannan from S. cerevisiae via mild periodate oxidation we generated hypoallergenic Bet-mannan neoglycoconjugates, which efficiently targeted CD14+ dendritic cells and Langerhans cells in human skin explants. Mannan conjugation resulted in sustained release from the skin and retention in secondary lymphoid organs, whereas unconjugated antigen showed fast renal clearance. In a mouse model, Bet-mannan neoglycoconjugates applied via laser-microporated skin synergistically elicited potent humoral and cellular immune responses, superior to intradermal injection. The induced antibody responses displayed IgE-blocking capacity, highlighting the therapeutic potential of the approach. Moreover, application via micropores, but not by intradermal injection, resulted in a mixed TH1/TH17-biased immune response. Our data clearly show that applying mannan-neoglycoconjugates to an organ rich in dendritic cells using laser-microporation is superior to intradermal injection. Due to their low IgE binding capacity and biodegradability, mannan neoglycoconjugates therefore represent an attractive formulation for allergen-specific epicutaneous immunotherapy.",
keywords = "C type lectin receptors, Dendritic cell targeting, Epicutaneous immunization, Hypoallergen, Laser microporation, Mannan, Skin vaccination, Specific immunotherapy",
author = "Yoan Machado and Sanne Duinkerken and Veronika Hoepflinger and Melissa Mayr and Evgeniia Korotchenko and Almedina Kurtaj and Isabel Pablos and Markus Steiner and Angelika Stoecklinger and Joyce L{\"u}bbers and Maximillian Schmid and Uwe Ritter and Sandra Scheiblhofer and Michael Ablinger and Verena Wally and Sarah Hochmann and Raninger, {Anna M.} and Dirk Strunk and {van Kooyk}, Yvette and Josef Thalhamer and Richard Weiss",
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month = "11",
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doi = "10.1016/j.jconrel.2017.09.020",
language = "English",
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pages = "87--99",
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Machado, Y, Duinkerken, S, Hoepflinger, V, Mayr, M, Korotchenko, E, Kurtaj, A, Pablos, I, Steiner, M, Stoecklinger, A, Lübbers, J, Schmid, M, Ritter, U, Scheiblhofer, S, Ablinger, M, Wally, V, Hochmann, S, Raninger, AM, Strunk, D, van Kooyk, Y, Thalhamer, J & Weiss, R 2017, 'Synergistic effects of dendritic cell targeting and laser-microporation on enhancing epicutaneous skin vaccination efficacy' Journal of Controlled Release, vol. 266, pp. 87-99. https://doi.org/10.1016/j.jconrel.2017.09.020

Synergistic effects of dendritic cell targeting and laser-microporation on enhancing epicutaneous skin vaccination efficacy. / Machado, Yoan; Duinkerken, Sanne; Hoepflinger, Veronika; Mayr, Melissa; Korotchenko, Evgeniia; Kurtaj, Almedina; Pablos, Isabel; Steiner, Markus; Stoecklinger, Angelika; Lübbers, Joyce; Schmid, Maximillian; Ritter, Uwe; Scheiblhofer, Sandra; Ablinger, Michael; Wally, Verena; Hochmann, Sarah; Raninger, Anna M.; Strunk, Dirk; van Kooyk, Yvette; Thalhamer, Josef; Weiss, Richard.

In: Journal of Controlled Release, Vol. 266, 28.11.2017, p. 87-99.

Research output: Contribution to journalArticleAcademicpeer-review

TY - JOUR

T1 - Synergistic effects of dendritic cell targeting and laser-microporation on enhancing epicutaneous skin vaccination efficacy

AU - Machado, Yoan

AU - Duinkerken, Sanne

AU - Hoepflinger, Veronika

AU - Mayr, Melissa

AU - Korotchenko, Evgeniia

AU - Kurtaj, Almedina

AU - Pablos, Isabel

AU - Steiner, Markus

AU - Stoecklinger, Angelika

AU - Lübbers, Joyce

AU - Schmid, Maximillian

AU - Ritter, Uwe

AU - Scheiblhofer, Sandra

AU - Ablinger, Michael

AU - Wally, Verena

AU - Hochmann, Sarah

AU - Raninger, Anna M.

AU - Strunk, Dirk

AU - van Kooyk, Yvette

AU - Thalhamer, Josef

AU - Weiss, Richard

PY - 2017/11/28

Y1 - 2017/11/28

N2 - Due to its unique immunological properties, the skin is an attractive target tissue for allergen-specific immunotherapy. In our current work, we combined a dendritic cell targeting approach with epicutaneous immunization using an ablative fractional laser to generate defined micropores in the upper layers of the skin. By coupling the major birch pollen allergen Bet v 1 to mannan from S. cerevisiae via mild periodate oxidation we generated hypoallergenic Bet-mannan neoglycoconjugates, which efficiently targeted CD14+ dendritic cells and Langerhans cells in human skin explants. Mannan conjugation resulted in sustained release from the skin and retention in secondary lymphoid organs, whereas unconjugated antigen showed fast renal clearance. In a mouse model, Bet-mannan neoglycoconjugates applied via laser-microporated skin synergistically elicited potent humoral and cellular immune responses, superior to intradermal injection. The induced antibody responses displayed IgE-blocking capacity, highlighting the therapeutic potential of the approach. Moreover, application via micropores, but not by intradermal injection, resulted in a mixed TH1/TH17-biased immune response. Our data clearly show that applying mannan-neoglycoconjugates to an organ rich in dendritic cells using laser-microporation is superior to intradermal injection. Due to their low IgE binding capacity and biodegradability, mannan neoglycoconjugates therefore represent an attractive formulation for allergen-specific epicutaneous immunotherapy.

AB - Due to its unique immunological properties, the skin is an attractive target tissue for allergen-specific immunotherapy. In our current work, we combined a dendritic cell targeting approach with epicutaneous immunization using an ablative fractional laser to generate defined micropores in the upper layers of the skin. By coupling the major birch pollen allergen Bet v 1 to mannan from S. cerevisiae via mild periodate oxidation we generated hypoallergenic Bet-mannan neoglycoconjugates, which efficiently targeted CD14+ dendritic cells and Langerhans cells in human skin explants. Mannan conjugation resulted in sustained release from the skin and retention in secondary lymphoid organs, whereas unconjugated antigen showed fast renal clearance. In a mouse model, Bet-mannan neoglycoconjugates applied via laser-microporated skin synergistically elicited potent humoral and cellular immune responses, superior to intradermal injection. The induced antibody responses displayed IgE-blocking capacity, highlighting the therapeutic potential of the approach. Moreover, application via micropores, but not by intradermal injection, resulted in a mixed TH1/TH17-biased immune response. Our data clearly show that applying mannan-neoglycoconjugates to an organ rich in dendritic cells using laser-microporation is superior to intradermal injection. Due to their low IgE binding capacity and biodegradability, mannan neoglycoconjugates therefore represent an attractive formulation for allergen-specific epicutaneous immunotherapy.

KW - C type lectin receptors

KW - Dendritic cell targeting

KW - Epicutaneous immunization

KW - Hypoallergen

KW - Laser microporation

KW - Mannan

KW - Skin vaccination

KW - Specific immunotherapy

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U2 - 10.1016/j.jconrel.2017.09.020

DO - 10.1016/j.jconrel.2017.09.020

M3 - Article

VL - 266

SP - 87

EP - 99

JO - Journal of Controlled Release

JF - Journal of Controlled Release

SN - 0168-3659

ER -