Influenza Virus-like Particles As Vaccines

流感病毒样颗粒作为疫苗

• 批准号: 7056094
• 负责人: JOSE M. GALARZA
• 金额: $ 49.98万
• 依托单位: TECHNOVAX, INC.
• 依托单位国家: 美国
• 财政年份: 2005
• 资助国家: 美国
• 起止时间: 2005-05-01 至 2007-12-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7056094
• 关键词: Baculoviridae; Sf9 cell line; active immunization; bioterrorism /chemical warfare; disease outbreaks; ferrets; genetic strain; influenza; influenza vaccines; inhalation drug administration; intramuscular injections; laboratory mouse; nonhuman therapy evaluation; recombinant virus; vaccine development; vaccine evaluation; vector vaccine; virus protein; viruslike particle

DESCRIPTION (provided by applicant): The long term objective of this proposal is to develop a novel cell-based system for creating influenza-virus like particle (VLP) vaccines against epidemic and potentially pandemic influenza viruses. This strategy will generate in a rapid and safe manner VLP structures that morphologically and biochemically resemble wild type virus, but are devoid of influenza genetic material and therefore non-infectious. Quadruple baculovirus recombinants will be used to express in insect cells the influenza structural proteins (M1, M2, HA, IMA) necessary for the formation and release of influenza VLPs from the cell surface. Replacement of the genes encoding the HA and NA, or both in the quadruple construct by those of the current epidemic (H3N2/Fujian) influenza virus or the HA and NA of influenza viruses with pandemic potential (H5N1, H7N7, and H1N1/1918) will allow us to create vaccines against these dangerous viruses in a safe manner. Candidate vaccines will be harvested and purified from the culture supernatant of insect cells infected with any of the four quadruple recombinants. The immunogenicity (local and systemic level) and protective efficacy elicited by these vaccines will be evaluated in mice and ferrets. Preliminary studies with a two component VLP vaccine in mice administered via either the intranasal or intramuscular route have demonstrated complete protection against a lethal influenza virus challenge. These results indicate the promise of this vaccine technology, which uses cell as production substrate, produces non-infectious entities, and is versatile enough to quickly accommodate emerging flu viruses. This will be a significant technological improvement in influenza vaccine production, and will facilitate the creation of vaccines against diverse influenza viruses and thereby protect the public from serious natural or perhaps intentional outbreaks of human influenza.

描述(由申请人提供)：这项提案的长期目标是开发一种新的基于细胞的系统，用于开发针对流行和可能大流行的流感病毒的类似流感病毒颗粒(VLP)疫苗。这一策略将以快速和安全的方式产生VLP结构，这些结构在形态和生物化学上与野生型病毒相似，但缺乏流感遗传物质，因此不具传染性。四重杆状病毒重组体将用于在昆虫细胞中表达流感结构蛋白(M1、M2、HA、IMA)，这些蛋白是流感病毒形成和从细胞表面释放所必需的。用目前流行的(H3N2/福建)流感病毒或具有大流行潜力的流感病毒(H5N1、H7N7和H1N1/1918)的HA和NA基因替换编码HA和NA的基因，或两者都在四重结构中，将使我们能够以安全的方式开发针对这些危险病毒的疫苗。候选疫苗将从感染了这四个四重组体中的任何一个的昆虫细胞的培养上清液中获得和提纯。这些疫苗的免疫原性(局部和系统水平)和保护效力将在小鼠和雪貂身上进行评估。通过鼻腔或肌肉途径给药的小鼠双组分VLP疫苗的初步研究表明，对致命性流感病毒的攻击具有完全的保护作用。这些结果表明了这种疫苗技术的前景，它使用细胞作为生产底物，生产非传染性实体，并且具有足够的通用性，足以迅速适应新出现的流感病毒。这将是流感疫苗生产方面的重大技术进步，并将促进针对各种流感病毒的疫苗的开发，从而保护公众免受严重的自然或可能故意爆发的人类流感的影响。