Influenza Virus-like Particles As Vaccines

流感病毒样颗粒作为疫苗

• 批准号: 6885636
• 负责人: JOSE M. GALARZA
• 金额: $ 51.02万
• 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 2007-04-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6885636
• 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（由申请方提供）：本提案的长期目标是开发一种新型基于细胞的系统，用于产生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。该策略将以快速和安全的方式产生VLP结构，其在形态学和生物化学上类似于野生型病毒，但缺乏流感遗传物质，因此不具有感染性。四重杆状病毒重组体将用于在昆虫细胞中表达流感病毒VLP形成和从细胞表面释放所必需的流感病毒结构蛋白（M1、M2、HA、IMA）。用目前流行的流感病毒（H3 N2/Fujian）的HA和NA或具有大流行潜力的流感病毒（H5 N1、H7 N7和H1N1/1918）的HA和NA替换编码HA和NA的基因或四重构建体中的HA和NA或两者的基因将允许我们以安全的方式产生针对这些危险病毒的疫苗。将从用四种四重重组体中的任一种感染的昆虫细胞的培养上清液中收获并纯化候选疫苗。将在小鼠和雪貂中评价这些疫苗引起的免疫原性（局部和全身水平）和保护效力。通过鼻内或肌内途径给药的双组分VLP疫苗在小鼠中的初步研究已经证明了对致死性流感病毒攻击的完全保护。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，产生非感染性实体，并且具有足够的通用性以快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，并将促进针对不同流感病毒的疫苗的创造，从而保护公众免受严重的自然或可能是故意的人类流感爆发的影响。