Preclinical Evaluation of a Novel Immunomodulatory Vaccine for Preventing and Treating HSV Infections

预防和治疗 HSV 感染的新型免疫调节疫苗的临床前评价

基本信息

批准号：
10600886
负责人：
Edward Gershburg
金额：
$ 28.81万
依托单位：
RATIONAL VACCINES, INC.
依托单位国家：
美国
项目类别：
财政年份：
2023
资助国家：
美国
起止时间：
2023-08-03 至 2024-07-31
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/10600886
关键词：
Acyclovir Address Animals Antiviral Agents Attenuated Axon Biological Cavia Centers for Disease Control and Prevention (U.S.)Cities Clinical Clinical Research Clinical Trials Collaborations Disease Disease Outbreaks Dose Encephalitis Engineering Exhibits Famciclovir Female Funding Future Genital Genitalia Goals Good Manufacturing Process Health Herpes Simplex Infections Herpes Simplex Virus Vaccines Herpesviridae Infections Herpesvirus 1 Human Human Herpesvirus 2 Immune response Immunization Immunize Individual Infection Intramuscular Investigational Drugs Investigational New Drug Application Laboratories Lesion Licensing Life Louisiana Macaca mulatta Measures Meningitis Molecular Virology Mus Neurologic Neurons Persons Pharmaceutical Preparations Pharmacology and Toxicology Phase Phase I Clinical Trials Play Population Process Production Records Regulatory Affairs Safety Sexually Transmitted Diseases Simplexvirus Small Business Innovation Research Grant Specific qualifier value Testing Therapeutic Tissues Toxic effect Toxicology Ulcer Universities Vaccinated Vaccine Production Vaccines Vagina Viral Load result Virulent Virus Virus Latency Virus Replication Virus Shedding Visual Work World Health Organization aged clinical material first-in-human genital herpes glycoprotein D-herpes simplex virus type 2 guinea pig model immunoregulation in vivo manufacture manufacturing process manufacturing scale-up novel novel vaccines preclinical evaluation preclinical safety preclinical study prevent product development prophylactic safety study scale up standard of care transmission process unvaccinated vaccine development vaccine efficacy vaccinology valacyclovir viral DNA

项目摘要

PROJECT SUMMARY: Herpes Simplex Virus (HSV) infections are common, infecting more than half of the world’s population. While most cases of genital herpes are caused by HSV type 2 (HSV-2), it is estimated that more than 150 million people aged 15-49 have genital HSV type 1 (HSV-1) infections. Although several vaccines have been evaluated for preventing/treating HSV infections, none have received FDA approval. Through an exclusive license with Louisiana State University, Rational Vaccines is developing a novel immunomodulatory vaccine engineered not to enter neuronal axons, rendering it incapable of establishing latency within the host. This vaccine was shown to be safe and effective at protecting female mice and guinea pigs from lethal intravaginal challenges with virulent HSV-1 and HSV-2. Further, this vaccine prevented HSV from establishing latency in vaccinated animals, and it induced prolonged immune responses in rhesus macaques. Moreover, the vaccine also exhibited therapeutic potential in guinea pigs latently infected with HSV-2. During the funding period of this Fast-Track proposal, Rational Vaccines will complete the studies required to submit an Investigational New Drug (IND) application to the FDA. In Phase I, process parameters will be developed, pilot batches of the RVx1001 will be manufactured, and product specifications will be drafted. This material will be used to validate the vaccine’s efficacy using the guinea pig model. Phase II will include IND-enabling GLP toxicology studies and scale-up production of the vaccine under current Good Manufacturing Practices (cGMP) to generate clinical trial material. The successful completion of the proposed work will extend to first-in-human clinical studies (beyond the scope of this proposal). Funding the development of this vaccine will play a key role in curbing the spread of HSV-associated conditions.

项目摘要：单纯疱疹病毒 (HSV) 感染很常见，感染了一半以上的人虽然大多数生殖器疱疹病例是由 2 型单纯疱疹病毒 (HSV-2) 引起，但据估计尽管有多种疫苗，但仍有超过 1.5 亿 15-49 岁的人患有生殖器 1 型单纯疱疹病毒 (HSV-1) 感染。已对预防/治疗 HSV 感染进行了评估，但尚未获得 FDA 批准。 Rational Vaccines 正在与路易斯安那州立大学合作开发一种新型免疫调节剂独家许可，Rational Vaccines 正在开发一种新型免疫调节剂疫苗被设计为不进入神经元轴突，使其无法在宿主体内建立潜伏期。这种疫苗被证明可以安全有效地保护雌性小鼠和豚鼠免受致命的感染此外，该疫苗还阻止了 HSV-1 和 HSV-2 的阴道内感染。它在恶性动物中具有潜伏期，并且在恒河猴中诱导了延长的免疫反应。在资助期间，疫苗还对潜伏感染 HSV-2 的豚鼠表现出治疗潜力。根据此快速通道提案，Rational Vaccines 将完成提交研究报告所需的研究向 FDA 提交新药 (IND) 申请在第一阶段，将开发工艺参数、试点批次。将制造 RVx1001，并起草产品规格，该材料将用于验证。该疫苗使用豚鼠模型的功效将包括支持 IND 的 GLP 毒理学研究和根据现行良好生产规范 (cGMP) 扩大疫苗生产规模以进行临床试验拟议工作的成功完成将扩展到首次人体临床研究（超越）。资助这种疫苗的开发将在遏制病毒传播方面发挥关键作用 HSV 相关病症。