DEVELOPMENT OF AN HA2 DOMAIN BASED PERIODONTITIS VACCINE

基于 HA2 结构域的牙周炎疫苗的开发

• 批准号: 6292948
• 负责人: ARTHUR A DECARLO
• 金额: $ 11.34万
• 依托单位: AGENTA BIOTECHNOLOGIES, INC.
• 依托单位国家: 美国
• 财政年份: 2001
• 资助国家: 美国
• 起止时间: 2001-04-01 至 2002-03-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6292948
• 关键词: Bacteroides gingivalis; bacterial proteins; bacterial vaccines; cysteine endopeptidases; hemagglutinin; host organism interaction; humoral immunity; immunoglobulin G; laboratory rat; molecular cloning; periodontium disorder; vaccine development

DESCRIPTION: ( Applicant's Abstract) Periodontal disease can be diagnosed in >50 percent of adults and may contribute to poor health through oral and systemic infection. The disease process is induced by bacteria and the severity of the disease seems due in large part to the immune response of the host. Over the past decades certain microorganisms have become highly implicated in the pathogenesis of periodontal disease including the gram negative Porphyromonas gingivalis (P. gingivalis). We have recently described and patented a small protein domain from P. gingivalis (HA2) that may be essential for the acquisition of iron and the porphyrin molecule, and, therefore, essential for survival of P. gingivalis in the periodontal pocket. Data indicated that the HA2 domain was detectable in clinical plaque samples and its detection was associated with hemoglobin binding activity within the plaque as well as with periodontal disease severity. Further, data indicated that an IgG humoral antibody response against the HA2 domain was stimulated with periodontal therapy and that this serum IgG could functionally inhibit hemoglobin-binding of the gingipains. These data implicate the HA2 domain of P. gingivalis as a good candidate for vaccine development to inhibit periodontal disease initiation and progression. PROPOSED COMMERCIAL APPLICATION: An effective vaccine against periodontal disease could be applicable to the entire population for the prevention of abatement of bone loss around the teeth that is often accompanied by acute abscess formation and loss of teeth. Notwithstanding malnourishment that accompanies partial or complete edentulism, periodontitis has significant untoward systemic effects so the value of this vaccine in terms of overall medical cost savings is enormous. Current treatment and prevention of periodontitis is ineffective or time-consuming and expensive.

描述：（申请人的摘要）牙周病可以是 在> 50%的成年人中被诊断出，并可能通过以下方式导致健康状况不佳： 口腔和全身感染。疾病过程是由细菌引起的， 疾病的严重性似乎在很大程度上是由于免疫反应的 主持人在过去的几十年里，某些微生物已经变得非常重要。 与牙周病的发病机制有关， 阴性牙龈卟啉单胞菌（牙龈卟啉单胞菌）。我们最近描述了 并申请了牙龈卟啉单胞菌（HA2）的一个小蛋白质结构域的专利， 对于铁和卟啉分子的获得至关重要，并且， 因此，对于牙龈卟啉单胞菌在牙周袋中的存活至关重要。 数据表明HA 2结构域在临床斑块样本中可检测到 它的检测与血红蛋白结合活性有关， 牙菌斑以及牙周病的严重程度。此外，数据显示， 刺激了针对HA2结构域的IgG体液抗体应答 牙周治疗，这种血清IgG可以功能性抑制 牙龈卟啉菌蛋白酶的血红蛋白结合。这些数据暗示了P的HA2结构域。 牙龈炎作为一种很好的候选疫苗开发，以抑制牙周 疾病的发生和发展。 拟定商业应用： 一种有效的预防牙周病的疫苗可能适用于整个 人口，以防止减少牙齿周围的骨质流失，这往往是 并伴有急性脓肿形成和牙齿脱落。 尽管 营养不良伴随部分或完全缺牙，牙周炎有 严重的不良全身反应，所以这种疫苗的价值，在整体而言， 医疗成本的节省是巨大的。 当前牙周炎的治疗和预防 是无效的或耗时且昂贵的。

项目成果

Humoral responses to Porphyromonas gingivalis gingipain adhesin domains in subjects with chronic periodontitis.

慢性牙周炎受试者对牙龈卟啉单胞菌牙龈蛋白酶粘附素结构域的体液反应。

• DOI: 10.1128/iai.72.3.1374-1382.2004
• 发表时间: 2004
• 期刊: Infection and immunity
• 影响因子: 3.1
• 作者: Nguyen,Ky-Anh;DeCarlo,ArthurA;Paramaesvaran,Mayuri;Collyer,CharlesA;Langley,DavidB;Hunter,Neil
• 通讯作者: Hunter,Neil