Preclinical Efficacy of a Capsid Virus-like Particle-Based Vaccine Targeting IL-1β for Treatment of Allergic Contact Dermatitis

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Hypersensitivity to a contact allergen is one of the most abundant forms of inflammatory skin disease. Today, more than 20% of the general population are sensitized to one or more contact allergens, making this disease an important healthcare issue, as re-exposure to the allergen can initiate the clinical disease termed allergic contact dermatitis (ACD). The current standard treatment using corticosteroids is effective, but it has side effects when used for longer periods. Therefore, there is a need for new alternative therapies for severe ACD. In this study, we used the versatile Tag/Catcher AP205 capsid virus-like particle (cVLP) vaccine platform to develop an IL-1β-targeted vaccine and to assess the immunogenicity and in vivo efficacy of the vaccine in a translational mouse model of ACD. We show that vaccination with cVLPs displaying full-length murine IL-1β elicits high titers of neutralizing antibodies, leading to a significant reduction in local IL-1β levels as well as clinical symptoms induced by treatment with 1-Fluoro-2,4-dinitrobenzene (DNFB). Moreover, we show that a single amino acid mutation in muIL-1β reduces the biological activity while maintaining the ability to induce neutralizing antibodies. Collectively, the data suggest that a cVLP-based vaccine displaying full-length IL-1β represents a promising vaccine candidate for use as an alternative treatment modality against severe ACD.

OriginalsprogEngelsk
Artikelnummer828
TidsskriftVaccines
Vol/bind10
Udgave nummer5
ISSN2076-393X
DOI
StatusUdgivet - 2022

Bibliografisk note

Funding Information:
Conflicts of Interest: A.F.S. and T.G.T are listed as co-inventors on a patent application covering the AP205 cVLP vaccine platform technology (WO2016112921 A1) licensed to AdaptVac. Employees of AdaptVac (L.G., A.F.S. and W.A.d.J.), a company working with virus-like particle display technology and vaccine development, including several patents. These data were partially supported by an unrestricted grant by the LEO Foundation. The LEO Foundation has no influence on this data, and the research conducted at the LEO Foundation Skin Immunology Research Center is fully independent of the LEO Foundation. The other authors have no financial conflict of interest.

Funding Information:
Funding: This research was supported by Innovations Fund Denmark, grant number 8053-00175B.

Publisher Copyright:
© 2022 by the authors. Licensee MDPI, Basel, Switzerland.

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