TY - JOUR

T1 - Preclinical Efficacy of a Capsid Virus-like Particle-Based Vaccine Targeting IL-1β for Treatment of Allergic Contact Dermatitis

AU - Goksøyr, Louise

AU - Funch, Anders B.

AU - Okholm, Anna K.

AU - Theander, Thor G.

AU - de Jongh, Willem Adriaan

AU - Bonefeld, Charlotte M.

AU - Sander, Adam F.

N1 - Publisher Copyright: © 2022 by the authors. Licensee MDPI, Basel, Switzerland.

PY - 2022

Y1 - 2022

N2 - 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.

AB - 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.

KW - allergic contact dermatitis

KW - AP205

KW - IL-1β

KW - vaccine

KW - virus-like particle

U2 - 10.3390/VACCINES10050828

DO - 10.3390/VACCINES10050828

M3 - Journal article

AN - SCOPUS:85132569275

VL - 10

JO - Vaccines

JF - Vaccines

SN - 2076-393X

IS - 5

M1 - 828

ER -