WISIT vaccines based on IL-31-derived peptides as a novel therapeutic approach for chronic pruritic dermatoses.

Vaccines are a promising therapy for the treatment of chronic conditions such as pruritus. IL-31 has been identified as an important mediator of itch. By targeting IL-31 signaling with immunotherapy, CP can be effectively alleviated. However, self-antigens such as IL-31 are highly tolerated, which has rendered conventional conjugate vaccines (CCVs) ineffective at generating sufficient antibody (Ab) responses to alleviate CP. Novel Win the Skin Immune System Trick (WISIT) vaccines however have been shown to induce substantially stronger Ab responses than CCVs in Parkinson's Disease, and so may be capable of overcoming IL-31 tolerance to effectively treat CP. In this report, WISIT vaccines presenting ten different IL-31-specific peptides were compared to CCVs presenting the same peptides. Multiple response parameters were assessed, including Ab titers induced, avidity of these Abs, and IL-31 signaling inhibition. Results demonstrated that WISIT vaccines outperform CCVs across all investigated metrics, culminating in the identification of 3 promising candidate WISIT vaccines to be taken forward for further clinical development. This report thus provides evidence that the improved immunogenicity of WISIT vaccines is not disease-specific and that WISIT vaccines may also be translated to treat dermatological disorders. Further preclinical development will be necessary to prepare the identified IL-31 targeting WISIT vaccine candidates for clinical testing.