青春痘疫苗抑制皮膚微生物相內痤瘡桿菌;Vaccines Targeting P. Acnes in the Skin Microbiome

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Title:	青春痘疫苗抑制皮膚微生物相內痤瘡桿菌;Vaccines Targeting P. Acnes in the Skin Microbiome
Authors:	黃俊銘
Contributors:	國立中央大學生醫科學與工程學系
Keywords:	青春痘;青春痘疫苗;痤瘡桿菌;發炎反應;;Acne vaccine;P. acnes;Acne vulgaris;Inflammation
Date:	2020-01-13
Issue Date:	2020-01-13 14:16:19 (UTC+8)
Publisher:	科技部
Abstract:	本計畫將利用疫苗降低痤瘡桿菌(P. acnes)引起的發炎而不引響皮膚表面微生物的平衡，這概念將是一個新的平台。控制皮膚共生菌引起的人類疾病。雖然抗生素是醫生處方進而治療大部分共生菌引起的疾病，包括青春痘，抗生素可引起抗藥性細菌且破壞微生物相的平衡，我們本計畫的青春痘疫苗將降低P. acnes引起的發炎而不影響皮膚菌相的平衡，我們最近發表的文章證實P. acnes的 CAMP factor 毒素可引起抗體反應，用大腸桿菌表達大量 CAMP factor 毒素當疫苗在老鼠上可提供對P. acnes引起發炎的保護作用。本計畫實驗設計考量P. acnes與人類的關係，包括 CAMP factor 毒素在青春痘的病理關係，使用臨床用的Alum當佐劑，即把P. acnes當作人類的共生菌。目標1，我們將決定P. acnes的數量與抗體表達的關係，獲得P. acnes引起的專一發炎反應。目標2，我們將誘發一種高且持久的抗體反應，並且執行治療性疫苗作用以避免青春痘復發。目標3，我們將評估抗體的專一性及副作用及調查人類血液中已經存在的抗體對疫苗的有效性，我們的青春痘疫苗將降低發炎中和毒素，而不直接殺死P. acnes及不影響人類皮膚微生物相的平衡。 ;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.
Relation:	財團法人國家實驗研究院科技政策研究與資訊中心
Appears in Collections:	[Department of Biomedical Sciences and Engineering ] Research Project

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