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

基本信息

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
项目类别：
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

项目摘要

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.

项目摘要对单纯疱疹病毒（HSV）疫苗的需求未满足。我们建议基于我们的R2技术平台开发实时衰减的HSV-2疫苗。 R2 疫苗在动物模型中显示出前所未有的安全性和功效，并提供抗原性优于亚基/mRNA和单一疫苗设计。 R2疫苗也是第一个缺乏神经侵染剂的活体α- 潜力，因此无法在神经中建立终身感染系统。在此快速轨道应用程序的I期中，我们建议：（i）产生HSV- 2低音临床分离株的自我口气感染克隆，（ii）使用克隆产生HSV-2 R2重组，（iii）通过与我们现有的HSV-1 R2疫苗候选者有关。在II期，HSV-2 R2疫苗将测试小鼠和豚鼠的安全性，免疫原性和功效。这项工作将为将产品开发推向临床试验提供基础。