# Establishment of a Dynamic Ear Inflammation Model in Rats for Acne Vulgaris and Evaluation of Adjuvanted Inactivated Cutibacterium acnes-Based Vaccines Efficacy

## TL;DR

Researchers created a rat model of acne inflammation and tested vaccines that target the bacteria responsible for acne, showing promising results in reducing inflammation and bacterial load.

## Contribution

A novel rat ear inflammation model for acne and evaluation of adjuvanted inactivated C. acnes vaccines for acne treatment.

## Key findings

- Inflammation in the rat ear model peaked within 1-3 days and resolved by day 7 with bacterial clearance.
- Vaccinated rats showed higher IgG levels, reduced swelling, and lower bacterial burden upon challenge.
- Vaccine-induced protection was linked to humoral immunity and suppression of inflammatory mediators.

## Abstract

Background/Objectives: Acne vulgaris is a chronic inflammatory skin disorder characterized by sebaceous gland hyperactivity, follicular hyperkeratinization, proliferation of Cutibacterium acnes (C. acnes), and subsequent inflammation. The development of effective therapeutics necessitates reliable preclinical models that accurately replicate key pathological aspects of the human disease. Methods: In this study, we established an inflammatory acne model in Wistar rats via the intradermal injection of live C. acnes into the ear pinnae and thoroughly characterized its temporal dynamics of the induced inflammation. Utilizing this model, we evaluated the protective efficacy of a whole-cell inactivated C. acnes vaccine (HI-C. acnes) formulated with adjuvants WS03 or MA107b. Results: Inflammation peaked between days 1 and 3 post-infection, manifesting as pronounced erythema, ear swelling, increased ear thickness, elevated bacterial load, and significant upregulation of pro-inflammatory cytokines (IL-6, IL-1β, and MCP-1). Histopathological examination revealed extensive neutrophil infiltration and microabscess formation, while immunohistochemistry confirmed localized overexpression of TNF-α, IL-1β, and CXCL1 within the lesional tissue. Inflammatory manifestations gradually subsided by day 5 and were fully resolved by day 7, which coincided with complete bacteria clearance and normalization of pro-inflammatory cytokine levels. Vaccinated rats developed significantly higher C. acnes-specific IgG titers and, upon challenge, exhibited markedly reduced ear swelling, diminished bacterial burden, and suppressed expression of key inflammatory mediators compared to control groups, indicating that vaccine-induced protection is associated with humoral immunity. Conclusions: Collectively, our standardized and quantifiable rat ear inflammation model provides a robust platform for mechanistic investigations and preclinical assessment of novel anti-acne vaccines and therapeutic agents.