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）：该提案的长期目标是开发一种新型的基于细胞的系统，用于制造针对流行性和潜在大流行性流感病毒的流感病毒样颗粒（VLP）疫苗。该策略将以快速、安全的方式生成 VLP 结构，其在形态和生化上类似于野生型病毒，但缺乏流感遗传物质，因此不具有传染性。四重杆状病毒重组体将用于在昆虫细胞中表达流感病毒结构蛋白（M1、M2、HA、IMA），这是流感病毒颗粒从细胞表面形成和释放所必需的。用当前流行的（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 的基因替换四重构建体中的 HA 和 NA 或两者的基因，将使我们能够以安全的方式制造针对这些危险病毒的疫苗。候选疫苗将从感染四种四重重组体中任一种的昆虫细胞的培养上清液中收获和纯化。这些疫苗的免疫原性（局部和全身水平）和保护功效将在小鼠和雪貂中进行评估。通过鼻内或肌肉注射途径对小鼠进行两组分 VLP 疫苗的初步研究表明，该疫苗可以完全预防致命流感病毒的攻击。这些结果表明了这种疫苗技术的前景，该技术使用细胞作为生产基质，产生非传染性实体，并且具有足够的通用性，可以快速适应新出现的流感病毒。这将是流感疫苗生产的重大技术进步，并将促进针对多种流感病毒的疫苗的研制，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。