VAGINAL VACCINATION WITH HERPES TYPE-2 PROTEIN AND DNA

使用 2 型疱疹蛋白和 DNA 进行阴道疫苗接种

• 批准号: 2792873
• 负责人: MICHAEL L HOWELL
• 金额: $ 9.95万
• 依托单位: PROTEIN EXPRESS, INC.
• 依托单位国家: 美国
• 财政年份: 1999
• 资助国家: 美国
• 起止时间: 1999-09-01 至 2000-10-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/2792873
• 关键词: Herpesviridae vaccine; antibody titering; chimeric proteins; complementary DNA; dosage forms; glycoproteins; guinea pigs; herpes simplex virus 2; laboratory mouse; sexually transmitted diseases; transfection /expression vector; vaccine development; vagina; vector vaccine; virus DNA; virus protein

Genital herpes simplex virus-2 (HSV-2) is among the most common of sexually transmitted diseases in women. Recurrence of latent infection can be frequent. Perinatal fetal transmission results in heightened morbidity and mortality. Current treatment consists of antiviral chemotherapy that merely decreases symptom severity with minimal impact on the incidence of recurrence and transmission rates. Antivirals do not cure. Clinically effective vaccines against HSV-2, a desirable alternative, require parenteral injections, often with unapproved or poorly tolerated adjuvants. This proposal seeks to develop a novel vaginally-applied transmucosal vaccine against genital HSV-2. The proposed vaccine candidate is unique in that it aims to effectively stimulate both humoral and cellular immunity through two components, the cloned HSV-2 gD cDNA and its recombinant gene product, a surface glycoprotein required for viral attachment and infection of the host cell. Manufactured into a novel vaginal suppository delivery vehicle, the efficacy of this vaccine will be tested in animal models of genital HSV-2. Successful results will warrant additional studies to determine tolerance, safety, booster requirements and clinical utility through a larger second phase application. Definitive studies then can be designed to meet the ultimate goal of a well-tolerated, cost-effective improvement in the clinical control of genital HSV-2 as a commercial opportunity. PROPOSED COMMERCIAL APPLICATION Genital herpes simplex virus-2 is among the most common of sexually transmitted diseases in women. Each year, 70,000 new cases of primary infection and 20 million cases of recurrence are reported in the U.S. alone. The current therapy of choice, Acylocvir, is worth over a billion dollars a year. We anticipate that an easily-administered, effective vaccine will be highly profitable.

生殖器单纯疱疹病毒2型（HSV-2）是女性最常见的性传播疾病之一。 潜伏感染的复发可能是频繁的。 围产期胎儿传播导致发病率和死亡率升高。 目前的治疗包括抗病毒化疗，仅降低症状严重程度，对复发率和传播率的影响最小。 抗病毒药物不能治愈。 针对HSV-2的临床有效的疫苗是一种理想的替代方案，需要肠胃外注射，通常使用未经批准或耐受性差的佐剂。 该提案旨在开发一种新的阴道应用的针对生殖器HSV-2的经粘膜疫苗。所提出的候选疫苗的独特之处在于，它旨在通过两种组分有效地刺激体液和细胞免疫，即克隆的HSV-2 gD cDNA及其重组基因产物，一种病毒附着和感染宿主细胞所需的表面糖蛋白。 将该疫苗制成一种新型阴道栓剂递送载体，将在生殖器HSV-2动物模型中测试该疫苗的效力。 成功的结果将保证额外的研究，以确定耐受性，安全性，助推器的要求和临床效用，通过一个更大的第二阶段的应用。 然后可以设计连续性研究以满足作为商业机会的生殖器HSV-2的临床控制的良好耐受性、成本效益的改善的最终目标。生殖器疱疹病毒（HSV-2）是一种常见的性传播疾病。 每年，仅在美国就报告了70，000例原发性感染和2000万例复发病例。 目前的治疗选择，阿昔洛韦，价值超过十亿美元一年。 我们预计，一种易于管理、有效的疫苗将是非常有利可图的。