An R2 non-neuroinvasive herpes simplex virus type 2 vaccine

R2 非神经侵袭性单纯疱疹病毒 2 型疫苗

• 批准号: 10698921
• 负责人: Gregory Allan Smith
• 金额: $ 29.75万
• 依托单位: THYREOS, INC
• 依托单位国家: 美国
• 财政年份: 2023
• 资助国家: 美国
• 起止时间: 2023-05-01 至 2024-04-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/10698921
• 关键词: Ablation; Animal Model; Antibodies; Attenuated; Attenuated Vaccines; Award; Axonal Transport; Bacterial Artificial Chromosomes; Binding; Birth; Bulla; CD4 Positive T Lymphocytes; CD8-Positive T-Lymphocytes; Cavia; Cell Culture Techniques; Central Nervous System Diseases; Clinical; Clinical Trials; Code; Congenital herpes simplex; Dedications; Development; Disease; Encephalitis; Excision; Failure; Foundations; Fred Hutchinson Cancer Research Center; Gene Expression; Genes; Genetic; Genetic Recombination; Genital; Genitalia; Goals; Herpes Simplex Virus Vaccines; Herpesvirus 1; Human Herpesvirus 2; Immune response; Infection; Infectious Agent; Invaded; Life; Marker Vaccines; Marketing; Measures; Medical center; Messenger RNA; Methods; Modeling; Monitor; Mucous Membrane; Mus; Mutate; Mutation; Nervous System; Neurologic; Neurologic Deficit; Newborn Infant; Pain; Pediatric Hospitals; Persons; Phase; Phase I Clinical Trials; Phenotype; Population; Positioning Attribute; Preparation; Proteins; Recombinants; Recurrence; Safety; Serial Passage; Serology; Sexual Transmission; Sexually Transmitted Diseases; Side; Small Business Technology Transfer Research; Stains; T cell response; Technology; Testing; Tissues; Universities; Vaccine Design; Vaccines; Vagina; Validation; Vertical Disease Transmission; Virulence; Virus; Virus Replication; Work; adaptive immune response; antibody-dependent cell cytotoxicity; antibody-dependent cellular phagocytosis; attenuation; cytokine; design; genital infection; guinea pig model; immunogenicity; latent infection; mouse model; mutant; neonate; neutralizing antibody; next generation; pre-clinical; product development; prototype; research and development; safety testing; technology platform; transmission process; vaccine candidate; vaccine development; vaccine efficacy

PROJECT SUMMARY There is an unmet need for a herpes simplex virus (HSV) vaccine. We propose to develop a live-attenuated HSV-2 vaccine based on our R2 technology platform. R2 vaccines show unprecedented safety and efficacy in animal models, and offer antigenicity superior to subunit/mRNA and single-round vaccine designs. R2 vaccines are also the first live-attenuated alphaherpesvirus vaccines that lack neuroinvasive potential, and thereby are incapable of establishing life-long infections in the nervous system. In phase I of this fast-track STTR application, we propose to: (i) produce a HSV- 2 self-excising infectious clone of a low-passage clinical isolate, (ii) use the clone to produce a HSV-2 R2 recombinant, and (iii) characterize the R2 vaccine in culture side by side with our existing HSV-1 R2 vaccine candidate. In phase II, the HSV-2 R2 vaccine will be tested for safety, immunogenicity, and efficacy in mice and guinea pigs. This work will provide the foundation to advance product development to clinical trials.

项目摘要 存在对单纯疱疹病毒（HSV）疫苗的未满足的需求。我们建议 基于我们的R2技术平台开发HSV-2减毒活疫苗。R2 疫苗在动物模型中显示出前所未有的安全性和有效性，并提供 抗原性上级于亚单位/mRNA和单轮疫苗设计。R2疫苗 也是第一个没有神经侵袭性的减毒活α疱疹病毒疫苗， 潜在的，从而无法建立终身感染的神经 系统在这个快速STTR应用的第一阶段，我们建议：（i）生产HSV- 2低传代临床分离株的自切除感染性克隆，（ii）使用该克隆 产生HSV-2 R2重组体，和（iii）在培养物侧表征R2疫苗， 我们现有的HSV-1 R2候选疫苗。在第二阶段，HSV-2 R2疫苗 将在小鼠和豚鼠中测试安全性、免疫原性和有效性。这项工作 将为推进产品开发到临床试验提供基础。