VAGINAL VACCINATION WITH HERPES TYPE-2 PROTEIN AND DNA

生殖器单纯疱疹病毒-2 （HSV-2）是女性中最常见的性传播疾病之一。潜伏性感染可频繁复发。围产期胎儿传播导致发病率和死亡率增高。目前的治疗包括抗病毒化疗，仅能减轻症状严重程度，对复发率和传播率的影响最小。抗病毒药物不能治愈。临床有效的2型单纯疱疹病毒疫苗是一种理想的替代方案，需要肠外注射，通常使用未经批准或耐受性差的佐剂。本提案旨在开发一种新的阴道应用经黏膜疫苗，以对抗生殖器HSV-2。该候选疫苗的独特之处在于，它旨在通过克隆的HSV-2 gD cDNA及其重组基因产物（病毒附着和感染宿主细胞所需的表面糖蛋白）两种成分有效地刺激体液和细胞免疫。该疫苗被制成一种新型阴道栓剂运载工具，其有效性将在生殖器HSV-2动物模型中进行测试。成功的结果将保证进一步的研究，以确定耐受性，安全性，加强要求和临床应用，通过更大的二期应用。然后，可以设计确定的研究，以实现最终目标，即在生殖器HSV-2的临床控制中获得耐受性良好、成本效益高的改进，并将其作为商业机会。单纯生殖器疱疹病毒-2是女性中最常见的性传播疾病之一。仅在美国，每年就有7万例新的原发性感染病例和2000万例复发病例。目前的首选疗法阿昔洛韦每年的价值超过10亿美元。我们预计，一种易于使用、有效的疫苗将带来高额利润。

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.