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.

单纯疱疹病毒（HSV）感染是常见的，感染了一半以上的人。 世界人口。虽然大多数生殖器疱疹病例是由HSV 2型（HSV-2）引起的，但据估计， 超过1.5亿15-49岁的人患有生殖器HSV 1型（HSV-1）感染。虽然有几种疫苗 已经被评估用于预防/治疗HSV感染，没有一个获得FDA批准。通过 与路易斯安那州州立大学的独家许可，理性疫苗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，使其不能在宿主内建立潜伏期。 这种疫苗被证明是安全和有效的，在保护雌性小鼠和豚鼠从致命的 阴道内用毒性HSV-1和HSV-2攻击。此外，该疫苗防止HSV建立 潜伏期，并诱导恒河猴免疫反应延长。而且 疫苗在潜伏感染HSV-2的豚鼠中也显示出治疗潜力。在供资期间 在这一快速通道提案中，理性疫苗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， 将生产RIGHT 1001，并起草产品规格。该材料将用于验证 用豚鼠模型研究疫苗的效力。II期将包括IND使能GLP毒理学研究， 根据现行药品生产质量管理规范（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扩展到首次人体临床研究（超过 本提案的范围）。资助这种疫苗的开发将在遏制艾滋病传播方面发挥关键作用。 HSV相关疾病。