Development of Chimeric Vesiculo/Alphaviruses as an Alphavirus Vaccine

嵌合水泡/甲病毒作为甲病毒疫苗的开发

• 批准号: 8698997
• 负责人: John Hayward Eldridge
• 金额: $ 115.66万
• 依托单位: YALE UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2013
• 资助国家: 美国
• 起止时间: 2013-08-08 至 2015-07-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8698997
• 关键词: Africa; Alphavirus; Alphavirus Infections; Attenuated; CD8B1 gene; Cell secretion; Cells; Characteristics; Chikungunya virus; Clinical; Cyclic GMP; Development; Disease; Dose; Drug Formulations; Drug or chemical Tissue Distribution; Effectiveness; Epidemic; Europe; FDA approved; Familiarity; Fever; Freeze Drying; Genes; Genetic; Goals; Human; Immune; Intramuscular; Laboratories; Life; Macaca; Mayaro virus; Mediating; Membrane; Membrane Glycoproteins; Modeling; Mus; Public Health; Recombinants; Research; Role; Safety; Seeds; Southeastern Asia; T-Lymphocyte; Technology; Testing; Time; Universities; Vaccination; Vaccines; Vesicular stomatitis Indiana virus; Virus; Virus Diseases; attenuation; base; biodefense; cell mediated immune response; chikungunya; env Gene Products; experience; immunogenicity; mouse model; neurovirulence; neutralizing antibody; nonhuman primate; prevent; protective efficacy; protein expression; vaccine candidate; vaccine development; vector; vector biodistribution; vector vaccine; vector-based vaccine; virus envelope

DESCRIPTION (provided by applicant): There is major public health concern about the continuing spread of alphaviruses such as chikungunya virus (CHIKV) that has caused major epidemics spreading from Africa and Southeast Asia to Europe. An ideal alphavirus vaccine would provide single-dose protection. A chimeric vaccine vector based on a defective vesicular stomatitis virus (VSV) deleted for its surface glycoprotein gene (G), and instead expressing the CHIKV envelope proteins induces high levels of CHIKV neutralizing antibodies and provides single-dose protection. The overall goal of this highly collaborative partnership is to preclinicaly validate this existing vaccine candidate as well as other highly attenuated VSV-vectored CHIKV vaccines in a recombinant VSV background that is already FDA-approved. The optimal rVSV/CHIKV vaccine candidate with the best combination of protective efficacy, manufacturability, attenuation, FDA familiarity, and clinical experience will then be selected. Thi candidate will be advanced through the development of compliant seed stocks documented to be appropriate for further manufacture under cGMP. In addition, this vaccine will be tested in non-human primates (NHPs) to confirm safety and efficacy, and a lyophilized formulation with the stability characteristics required for practical field use will be developed. General applicability of the platform for another emerging alphavirus will also be tested.

描述（由申请人提供）：基孔肯雅病毒（CHIKV）等甲病毒的持续传播引起了重大公共卫生担忧，该病毒已导致重大流行病从非洲和东南亚蔓延至欧洲。理想的甲病毒疫苗将提供单剂量保护。一种基于缺陷性水泡性口炎病毒 (VSV) 的嵌合疫苗载体，其表面糖蛋白基因 (G) 被删除，并表达 CHIKV 包膜蛋白，可诱导高水平的 CHIKV 中和抗体并提供单剂量保护。这一高度合作伙伴关系的总体目标是在已获得 FDA 批准的重组 VSV 背景下对现有候选疫苗以及其他高度减毒 VSV 载体的 CHIKV 疫苗进行临床前验证。然后将选择具有保护功效、可制造性、减毒、FDA 熟悉度和临床经验最佳组合的最佳 rVSV/CHIKV 候选疫苗。该候选产品将通过开发符合 cGMP 记录的合规种子库存来推进，这些种子库存适合在 cGMP 下进一步生产。此外，该疫苗还将在非人灵长类动物（NHP）中进行测试，以确认安全性和有效性，并将开发具有实际现场使用所需的稳定性特征的冻干制剂。该平台对另一种新兴甲病毒的普遍适用性也将得到测试。