Evaluation of single-strain Prevotella histicola on KLH-driven immune responses in healthy volunteers: A randomized controlled trial with EDP1815

Abstract

IntroductionEDP1815 is a single-strain of Prevotella histicola with preclinical immunomodulatory properties. The aim of this study was to evaluate pharmacodynamic effects of EDP1815 on the immune response following immunization with keyhole limpet hemocyanin (KLH) and dermal rechallenge. MethodsThirty-two healthy subjects (median 30, range 18–59 years) were randomized over two cohorts to EDP1815 or placebo (12:4). Both cohorts received 8.0 × 1011 total cells daily for 28 days, reconstituted in 10 (A formulation) or 5 (B formulation) capsules. KLH-specific antibodies and circulating regulatory T cells were evaluated. Skin response after rechallenge was assessed with imaging. Immune cell subsets from blister exudates were assessed in the B cohort only. Ex vivo phytohemagglutinin and lipopolysaccharide whole blood challenges were performed to evaluate cytokine release. Gastrointestinal tract persistence, prevalence, and colonization of EDP1815 were assessed by fecal qPCR and microbiome assays. Data were analyzed using repeated measures analysis of covariances. ResultsThere was a trend toward a treatment effect on the KLH-induced skin rechallenge response (CIELab a* estimated difference (ED) −1.50 arbitrary unit (AU), 95% CI −3.47–0.47 AU, P = .13, and average redness ED −0.14 AU, 95% CI −0.31–0.03 AU, P = .10 in B cohort) and, to a lesser extent, on the humoral KLH response. No notable EDP1815 effects were observed on gut persistence, microbiome, and other safety parameters. ConclusionBased on our findings and the clinical benefit observed in the phase 2 study in psoriasis, further investigation of the immunomodulatory effects and potential clinical benefit of EDP1815 is warranted.