Laser-facilitated epicutaneous immunotherapy with hypoallergenic beta-glucan neoglycoconjugates suppresses lung inflammation and avoids local side effects in a mouse model of allergic asthma

Evgeniia Korotchenko; Viktoria Schießl; Sandra Scheiblhofer; Mario Schubert; Elfriede Dall; Isabella A Joubert; Helen Strandt; Theresa Neuper; Muamera Sarajlic; Renate Bauer; Mark Geppert; David Joedicke; Sabrina Wildner; Susanne Schaller; Stephan Winkler; Gabriele Gadermaier; Jutta Horejs-Hoeck; Richard Weiss

doi:10.1111/all.14481

Laser-facilitated epicutaneous immunotherapy with hypoallergenic beta-glucan neoglycoconjugates suppresses lung inflammation and avoids local side effects in a mouse model of allergic asthma

Allergy. 2021 Jan;76(1):210-222. doi: 10.1111/all.14481. Epub 2020 Jul 16.

Authors

Evgeniia Korotchenko¹, Viktoria Schießl¹, Sandra Scheiblhofer¹, Mario Schubert¹, Elfriede Dall¹, Isabella A Joubert¹, Helen Strandt¹, Theresa Neuper¹, Muamera Sarajlic¹, Renate Bauer¹, Mark Geppert¹, David Joedicke², Sabrina Wildner¹, Susanne Schaller², Stephan Winkler², Gabriele Gadermaier¹, Jutta Horejs-Hoeck¹, Richard Weiss¹

Affiliations

¹ Department of Biosciences, University of Salzburg, Salzburg, Austria.
² Research and Development, University of Applied Biosciences Upper Austria, Hagenberg, Austria.

Abstract

Background: Allergen-specific immunotherapy via the skin targets a tissue rich in antigen-presenting cells, but can be associated with local and systemic side effects. Allergen-polysaccharide neoglycogonjugates increase immunization efficacy by targeting and activating dendritic cells via C-type lectin receptors and reduce side effects.

Objective: We investigated the immunogenicity, allergenicity, and therapeutic efficacy of laminarin-ovalbumin neoglycoconjugates (LamOVA).

Methods: The biological activity of LamOVA was characterized in vitro using bone marrow-derived dendritic cells. Immunogenicity and therapeutic efficacy were analyzed in BALB/c mice. Epicutaneous immunotherapy (EPIT) was performed using fractional infrared laser ablation to generate micropores in the skin, and the effects of LamOVA on blocking IgG, IgE, cellular composition of BAL, lung, and spleen, lung function, and T-cell polarization were assessed.

Results: Conjugation of laminarin to ovalbumin reduced its IgE binding capacity fivefold and increased its immunogenicity threefold in terms of IgG generation. EPIT with LamOVA induced significantly higher IgG levels than OVA, matching the levels induced by s.c. injection of OVA/alum (SCIT). EPIT was equally effective as SCIT in terms of blocking IgG induction and suppression of lung inflammation and airway hyperresponsiveness, but SCIT was associated with higher levels of therapy-induced IgE and TH2 cytokines. EPIT with LamOVA induced significantly lower local skin reactions during therapy compared to unconjugated OVA.

Conclusion: Conjugation of ovalbumin to laminarin increased its immunogenicity while at the same time reducing local side effects. LamOVA EPIT via laser-generated micropores is safe and equally effective compared to SCIT with alum, without the need for adjuvant.

Keywords: dendritic cell targeting; epicutaneous immunotherapy; glycoconjugates; laser; skin vaccination.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Allergens
Animals
Asthma* / therapy
Lasers
Mice
Mice, Inbred BALB C
Ovalbumin
Pneumonia*
beta-Glucans*

Substances

Allergens
beta-Glucans
Ovalbumin