The overall goal is to introduce a vaccination approach that can reduce Propionibacterium acnes (P. acnes), also named as Cutibacterium acnes (C. acnes)-associated inflammation without disturbing the bacterial ecosystem on the surface of skin. The concept of reducing inflammation while keeping bacteria at an optimal balance would set a standard platform for controlling the human diseases caused by commensal bacteria. Although antibiotics have been commonly prescribed for treating most commensal-associated diseases including acne vulgaris, they pose the risk of promoting bacterial resistance and disrupting the natural ecological balance of commensal bacteria in the human micorbiome. In this proposal, we outline a vaccination approach for treatment of acne vulgaris. Our approach will reduce the degree of P. acnes-associated inflammation without disrupting the normal body flora. Our publications have demonstrated that the Christie-Atkins-Munch-Peterson (CAMP) factor of P. acnes is an immunogenic and secretory toxin. Immunization of mice with E. coil over-expressing CAMP factor provides therapeutic protection against P. acnes. With the goal of using vaccination approaches for acne treatment in the future, many experiments in this proposal are designed to further assess the relationship of P. acnes in humans. These experiments include investigation of the role of CAMP factor in acne pathogenesis and vaccination with a clinical adjuvant (alum), and consideration of the status of P. acnes as commensal bacteria in humans.Three Specific Aims are proposed. In the Specific Aim 1, we will determine the correlation between the titer of antibody to CAMP factor and the number of P. acnes colonization in mice, and obtain a P. acnes-specific inflammatory profile. In the Specific Aim 2, we will provoke a persistent and high antibody response to enhance the preventive effect of CAMP factor vaccination against P. acnes-induced inflammation and perform therapeutic vaccination to circumvent acne recurrence. In the Specific Aim 3, we will assess the antibody specificity and evaluate the possible side-effects of vaccination targeting CAMP factor, and evaluate the impact of pre-existing antibodies to P. acnes on the immunity induced by CAMP factor vaccination. Rather than directly killing P. acnes, we propose a vaccination approach by neutralizing the P. acnes secretory toxin which is the source of inflammation. This approach will suppress the source of acne inflammation without disrupting the status of P. acnes as a commensal bacterium in the human microbiome.
|Effective start/end date||1/08/21 → 31/07/22|
In 2015, UN member states agreed to 17 global Sustainable Development Goals (SDGs) to end poverty, protect the planet and ensure prosperity for all. This project contributes towards the following SDG(s):