Acne Vaccines Targeting a Surface Sialidase and a Secreted CAMP Factor Toxin

针对表面唾液酸酶和分泌的 CAMP 因子毒素的痤疮疫苗

• 批准号: 7482001
• 负责人: CHUN-MING HUANG
• 金额: $ 10万
• 依托单位: VAXIN INC.
• 依托单位国家: 美国
• 财政年份: 2008
• 资助国家: 美国
• 起止时间: 2008-09-05 至 2010-08-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7482001
• 关键词: Acne; Acne Vulgaris; Adjuvant; Adverse effects; Aerobic; Affect; Animal Model; Antibiotic Resistance; Antibiotic Therapy; Antibiotics; Antibodies; Antigens; Apoptosis; Bacteria; Bacterial Drug Resistance; Biological Assay; Cell Wall; Cicatrix; Condition; Congenital Abnormality; Data; Development; Disease; Ear; Equilibrium; Excision; Figs - dietary; Genome; Genomics; Goals; Growth; Homeostasis; Hormones; Human; Immune; Immune response; Immunity; Immunoglobulin G; In Vitro; Infection; Inflammation; Inflammatory; Intraperitoneal Injections; Isotretinoin; Laboratories; Lead; Lesion; Life; Measures; Medicine; Mental Depression; Mental disorders; Microbe; Modality; Modeling; Mus; Neuraminidase; Organism; Pathogenesis; Patients; Personal Satisfaction; Pharmaceutical Preparations; Population; Predisposition; Pregnant Women; Production; Propionibacterium acnes; Proteins; Proteome; Proteomics; Protocols documentation; Public Health; Rate; Reaction; Reporting; Resistance; Retinoids; Risk; Risk Management; Role; Safety; Severities; Sialic Acids; Skin; Specificity; Staging; Staphylococcus aureus; Surface; Systemic Therapy; Therapeutic; Thick; Tissues; Toxin; United States Food and Drug Administration; Vaccinated; Vaccination; Vaccines; Virulence; Virulence Factors; Vitamin A; base; cell injury; hormone regulation; immunogenicity; in vivo; keratinocyte; killings; prevent; programs; psychologic; skin disorder; vector-based vaccine

DESCRIPTION (provided by applicant): Propionibacterium acnes (P. acnes) is most notably recognized for its role in acne vulgaris, the most common skin disease, affecting 85-100% of the population at some point in their lives. Current treatments for vulgaris acne using isotretinoin (13-cis-retinoic acid) or antibiotics can have many undesirable effects, including depression, teratogenicity, hormone imbalance and alteration of skin microflora. Due to the side effects, the Food and Drug Administration (FDA) has announced a strengthened risk management program to enhance safe use of isotretinoin for treating severe acne. Vaccines against acne vulgaris are not yet available. Two P. acnes proteins (a cell-wall anchoring sialidase and a secreted CAMP factor toxin) were selected as antigens for the development of acne vaccines. Our data demonstrated that the removal of sialic acids on the surface of human sebocytes by sialidase increased their susceptibility to P. acnes infection. In addition, CAMP factor, which induced apoptosis in keratinocytes, was up-regulated in P. acnes under anaerobic conditions. Thus, acne vaccines targeting sialidase and CAMP factor will be created in this proposal in comparison with killed P. acnes-based vaccines. We will construct acne vaccines that specifically suppress P. acnes-induced inflammation and minimize the risk of changing the homeostasis of resident skin microbes. The specific aims in this proposal will include 1) comparing various vaccination modalities to maximize the immunogenicities of sialidase and CAMP factor, 2) investigating in vitro/in vivo protective immunity of acne vaccines by neutralization assay and a newly-developed acne animal model, and 3) determining the specificity and safety of acne vaccines by detecting the susceptibility of vaccinated mice to various microbes. The quantitative milestones in this proposal will be to i) optimize a protocol to create the most potent acne vaccine for eliciting robust antibody (IgG) production; ii) screen various acne vaccine constructs in vivo; iii) measure the acne vaccine's immune protection against bacterial growth and inflammation; iv) select a P. acnes specific vaccine that significantly decreases P. acnes-induced inflammation v) without damaging the balance of skin microflora. PUBLIC HEALTH RELEVANCE More than fifty million people in the U.S. suffer from acne vulgaris. The association between Propionibacterium acnes (P. acnes) infection and the acne severity has been reported. Systemic therapies using antibiotics or the vitamin A-derived retinoids cause many side effects including hormone imbalance, mental disorders, and teratogenicity. The goal of this proposal is to develop systemically effective acne vaccines that can specifically suppress P. acnes-induced skin inflammation without disturbing the balance of skin flora.

描述（由申请人提供）：痤疮丙酸杆菌（P.痤疮）最著名的是其在痤疮的痤疮（最常见的皮肤病）中的作用，在他们生活中的某个时候影响了85-100％的人口。当前使用异维使用诺（13- cis-近红酸）或抗生素的脉冲痤疮治疗可能会产生许多不希望的作用，包括抑郁症，致死性，激素失衡和皮肤微生物的改变。由于副作用，食品药品监督管理局（FDA）宣布了一项加强风险管理计划，以增强同维诺蛋白在治疗严重痤疮方面的安全使用。尚未获得针对痤疮痤疮的疫苗。选择了两种痤疮蛋白（细胞壁锚定唾液酸酶和一个分泌的营地因子毒素）作为抗原开发痤疮疫苗。我们的数据表明，通过唾液酸酶在人果细胞表面去除唾液酸会增加其对痤疮疟原虫感染的敏感性。此外，在厌氧条件下诱导角质形成细胞凋亡的cAMP因子在痤疮疟原虫中被上调。因此，与基于痤疮疟原虫的疫苗相比，该提案将创建靶向唾液酸酶和cAMP因子的痤疮疫苗。我们将构建痤疮疫苗，这些疫苗专门抑制痤疮诱导的炎症，并最大程度地减少改变居民皮肤微生物稳态的风险。 The specific aims in this proposal will include 1) comparing various vaccination modalities to maximize the immunogenicities of sialidase and CAMP factor, 2) investigating in vitro/in vivo protective immunity of acne vaccines by neutralization assay and a newly-developed acne animal model, and 3) determining the specificity and safety of acne vaccines by detecting the susceptibility of vaccinated mice to various microbes.该提案中的定量里程碑将是i）优化一项方案，以创建最有效的痤疮疫苗，以引发鲁棒抗体（IgG）生产； ii）在体内筛选各种痤疮疫苗构建体； iii）测量痤疮疫苗的免疫保护抗细菌生长和炎症； iv）选择一种明显降低痤疮疟原虫诱导的炎症的特异性疫苗，而不会损害皮肤微生物的平衡。在美国，公共卫生相关性超过500万人患有痤疮。据报道，痤疮丙酸杆菌（P.痤疮）感染与痤疮严重程度之间的关联。使用抗生素或维生素A衍生的类维生素的全身疗法会引起许多副作用，包括激素失衡，精神障碍和致畸性。该提案的目的是开发具有系统有效的痤疮疫苗，这些疫苗可以特异性抑制痤疮假单胞菌引起的皮肤炎症，而不会干扰皮肤菌群的平衡。

项目成果

Vaccines and photodynamic therapies for oral microbial-related diseases.

• DOI: 10.2174/138920009787048365
• 发表时间: 2009-01
• 期刊: Current drug metabolism
• 影响因子: 2.3
• 作者: Liu PF;Zhu WH;Huang CM
• 通讯作者: Huang CM

Use of nanoparticles as therapy for methicillin-resistant Staphylococcus aureus infections.

使用纳米颗粒治疗耐甲氧西林金黄色葡萄球菌感染。

• DOI: 10.2174/138920009790274522
• 发表时间: 2009
• 期刊: Current drug metabolism
• 影响因子: 2.3
• 作者: Liu,Pei-Feng;Lo,Chih-Wei;Chen,Chao-Hsuan;Hsieh,Ming-Fa;Huang,Chun-Ming
• 通讯作者: Huang,Chun-Ming

Vaccination targeting surface FomA of Fusobacterium nucleatum against bacterial co-aggregation: Implication for treatment of periodontal infection and halitosis.

• DOI: 10.1016/j.vaccine.2010.02.047
• 发表时间: 2010-04-26
• 期刊: VACCINE
• 影响因子: 5.5
• 作者: Liu, Pei-Feng;Shi, Wenyuan;Zhu, Wenhong;Smith, Jeffery W.;Hsieh, Shie-Liang;Gallo, Richard L.;Huang, Chun-Ming
• 通讯作者: Huang, Chun-Ming

Vaccine therapy for P. acnes-associated diseases.

痤疮丙酸杆菌相关疾病的疫苗治疗。

• DOI: 10.2174/1871526510808030160
• 发表时间: 2008
• 期刊: Infectious disorders drug targets
• 作者: Nakatsuji,Teruaki;Rasochova,Lada;Huang,Chun-Ming
• 通讯作者: Huang,Chun-Ming

Proteomics integrated with Escherichia coli vector-based vaccines and antigen microarrays reveals the immunogenicity of a surface sialidase-like protein of Propionibacterium acnes.

• DOI: 10.1002/prca.200780103
• 发表时间: 2008-09
• 期刊: PROTEOMICS CLINICAL APPLICATIONS
• 影响因子: 2
• 作者: Huang, Cheng-Po;Liu, Yu-Tsueng;Nakatsuji, Teruaki;Shi, Yang;Gallo, Richard R.;Lin, Shwu-Bin;Huang, Chun-Ming
• 通讯作者: Huang, Chun-Ming