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

• 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
• 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

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，感染了超过一半的 世界人口。虽然大多数生殖器疱疹病例是由2型单纯疱疹病毒(HSV-2)引起的，但据估计 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。虽然有几种疫苗 已经进行了预防/治疗HSV感染的评估，没有一种获得FDA的批准。通过一个 获得路易斯安那州立大学的独家许可，Rational Vaccines正在开发一种新的免疫调节剂 疫苗被设计成不进入神经元轴突，使其无法在宿主内建立潜伏期。 这种疫苗被证明在保护雌性小鼠和豚鼠免受致命伤害方面是安全有效的。 阴道内感染强毒HSV-1和HSV-2。此外，这种疫苗阻止了HSV建立 在接种疫苗的动物中潜伏期，并在恒河猴中诱导延长免疫反应。此外， 疫苗对潜伏感染HSV-2的豚鼠也显示出治疗潜力。在资助期 在这个快速通道提案中，Rational Vaccines将完成提交调查报告所需的研究 向FDA提交新药(IND)申请。在第一阶段，将开发工艺参数，试生产批量的 将制造RVx1001，并起草产品规格。此材料将用于验证 用豚鼠模型研究疫苗的效力。第二阶段将包括支持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 材料。拟议工作的成功完成将延伸到首个人类临床研究(以后 这项提案的范围)。为这种疫苗的开发提供资金将在遏制霍乱传播方面发挥关键作用 单纯疱疹病毒相关条件。