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.acnes)因其在寻常痤疮中的作用而被公认，寻常痤疮是最常见的皮肤病，影响85%-100%的人在他们生命中的某个时候。目前使用异维A酸(13-顺式维甲酸)或抗生素治疗寻常痤疮可能会产生许多不良影响，包括抑郁、致畸、激素失衡和皮肤微生物区系改变。由于副作用，美国食品和药物管理局(FDA)宣布了一项加强风险管理计划，以提高异维A酸治疗严重痤疮的安全性。目前还没有针对寻常痤疮的疫苗。选择两种痤疮假单胞菌蛋白(细胞壁锚定唾液酸酶和分泌的cAMP因子毒素)作为抗原，用于研制痤疮疫苗。我们的数据表明，唾液酸酶去除人皮脂细胞表面的唾液酸增加了他们对痤疮假单胞菌感染的易感性。此外，在厌氧条件下，诱导角质形成细胞凋亡的cAMP因子在痤疮假单胞菌中上调。因此，在这项提案中，将创建针对唾液酸酶和cAMP因子的痤疮疫苗，与灭活的以痤疮假单胞菌为基础的疫苗相比。我们将构建专门抑制痤疮假单胞菌诱导的炎症的痤疮疫苗，并将改变常驻皮肤微生物的动态平衡的风险降至最低。这项建议的具体目的将包括：1)比较各种疫苗接种方式，以最大限度地提高唾液酸酶和cAMP因子的免疫原性；2)通过中和试验和新开发的痤疮动物模型来研究痤疮疫苗的体外/体内保护性免疫；3)通过检测接种的小鼠对各种微生物的敏感性来确定痤疮疫苗的特异性和安全性。这项建议中的量化里程碑将是：i)优化方案，以创建最有效的痤疮疫苗，以产生强大的抗体(IgG)；ii)在体内筛选各种痤疮疫苗结构；iii)测量痤疮疫苗对细菌生长和炎症的免疫保护；iv)选择一种可显著降低痤疮杆菌引起的炎症的特定疫苗；v)在不破坏皮肤微生物区系平衡的情况下。公共卫生关注点美国有超过5000万人患有寻常痤疮。痤疮丙酸杆菌感染与痤疮严重程度的关系已有报道。使用抗生素或维生素A衍生的维甲酸的全身治疗会导致许多副作用，包括激素失衡、精神障碍和致畸。这项提议的目标是开发系统有效的痤疮疫苗，这种疫苗可以在不破坏皮肤菌群平衡的情况下，特异性地抑制痤疮假单胞菌引起的皮肤炎症。

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