DNA vaccine effiicacy in Herpes Simplex Virus type 2

描述：（改编自申请人的摘要）单纯疱疹病毒2型 HSV-2感染是最常见的性传播疾病之一。 生殖道急性感染后，病毒变得潜伏， 可以重新激活引起复发性疾病或无症状地脱落。 因此，疫苗可以是预防性的，防止或改变免疫缺陷。 初始感染，或治疗，预防或最大限度地减少复发性疾病 那些曾经感染过HSV-2的人。迄今为止，这两种疫苗策略都没有 成功了最近的一种疫苗策略利用DNA，但这种方法 没有被优化。在本申请中，我们描述了设计成 提高HSV DNA疫苗的有效性。因为保护他们免受 急性和复发性HSV疾病似乎是由T细胞介导的， 目的是评估靶向的HSV-2糖蛋白B（gB）DNA疫苗 内体/溶酶体增加MHC II类呈递和CD 4+应答 (Aim 1）。我们还将表征针对蛋白酶体的gB DNA疫苗 增加MHC I类呈递和CD 8 + T细胞应答（目的2）。我们 将验证靶向，评估T细胞反应，并评估这些疫苗， 我们充分表征的HSV-2感染的小动物模型。在目标3中， 将联合收割机结合最好的MHC I类和MHC II类靶向疫苗， 评估其综合疗效。在目标4中，我们将研究 与免疫归巢受体共表达gB。通过靶向抗原 我们假设，我们将增加淋巴结中的呈递细胞， HSV特异性和先天性免疫应答和保护。我们的经验与 小鼠和豚鼠模型以及病毒学、临床和 免疫学终点使这些模型成为检查策略的理想模型， 提出了提出的实验将提高我们对 对急性和复发性疾病的保护性免疫反应，增加我们的 了解HSV-2和其他病原体的靶向DNA载体，并应 从而改进DNA疫苗。

DESCRIPTION: (Adapted from Applicant's Abstract) Herpes simplex virus type 2 (HSV-2) infection is one of the most common sexually transmitted diseases. Following acute infection of the genital tract, the virus becomes latent and can reactivate to cause recurrent disease or be shed asymptomatically. Therefore vaccines can either be prophylactic, preventing or modifying the initial infection, or therapeutic, preventing or minimizing recurrent disease in those previously infected with HSV-2. To date neither vaccine strategy has been successful. One recent vaccine strategy utilizes DNA but this approach has not been optimized. In this application, we describe experiments designed to increase the effectiveness of HSV DNA vaccines. Because protection from both acute and recurrent HSV disease appears to be mediated by T cells, the initial aims are to evaluate HSV-2 glycoprotein B (gB) DNA vaccines targeted to the endosome/lysosome to increase MHC class II presentation and the CD4+ response (Aim 1). We also will characterize gB DNA vaccines targeted to the proteasome to increase MHC Class I presentation and the CD8+ T cell response (Aim 2). We will verify targeting, evaluate T cell responses, and assess these vaccines in our well-characterized small animal models of HSV-2 infection. In Aim 3, we will combine the best MHC class I and MHC class II targeted vaccines and evaluate their combined efficacy. In Aim 4, we will examine the effects of co-expressing gB with immune homing receptors. By targeting the antigen presenting cells to the lymph nodes we hypothesize that we will increase both the HSV-specific and innate immune response and protection. Our experience with the murine and guinea pig models as well as the virologic, clinical and immunologic endpoints make these models ideal for examining the strategies proposed. The experiments proposed will improve our understanding of the protective immune response for acute and recurrent disease, increase our knowledge of targeted DNA vectors for HSV-2 and other pathogens, and should result in improved DNA vaccines.