Novel vaccines for broad protection against avian influenza

广泛预防禽流感的新型疫苗

• 批准号: 8228036
• 负责人: John K. Rose
• 金额: $ 40.55万
• 依托单位: YALE UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2009
• 资助国家: 美国
• 起止时间: 2009-03-15 至 2015-02-28
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8228036
• 关键词: Address; Antibodies; Antibody Formation; Antigens; Attenuated; Avian Influenza; Avian Influenza A Virus; CD4 Positive T Lymphocytes; CD8B1 gene; Canada; Clinical Trials; Collaborations; Complement; Cytotoxic T-Lymphocytes; Data; Development; Effectiveness; Future; Genes; Goals; HIV vaccine; Health; Hemagglutinin; Hong Kong; Human; Immunity; Influenza; Influenza A Virus, H5N1 Subtype; Laboratories; Length; Life; Lung; Methods; Mus; Mutation; Passive Transfer of Immunity; Play; Population; Positioning Attribute; Proteins; Publishing; Recombinants; Role; Solid; T-Cell Depletion; Testing; Time; United States National Institutes of Health; Vaccine Production; Vaccines; Vesicular stomatitis Indiana virus; Virus; Virus Diseases; base; experience; influenza virus strain; influenza virus vaccine; influenzavirus; killings; neutralizing antibody; nonhuman primate; novel; novel vaccines; pandemic disease; pandemic influenza; research study; response; vector; vector vaccine; vector-based vaccine

DESCRIPTION (provided by applicant): Highly pathogenic avian influenza (HPAI) viruses are likely to cause an influenza pandemic at some point in the future. Traditional methods of influenza vaccine production will probably be too slow to allow an effective response to such a pandemic. Development of rapidly deployable vaccine platforms capable of protecting against such a pandemic is therefore of major importance. Vaccine vectors based on recombinant live, attenuated or replication- defective vesicular stomatitis virus (VSV) are among the most potent vaccine vectors tested to date. They also have a major advantage in that there is no pre-existing immunity to the vector in the human population. VSV vectors expressing an H5N1 hemmaglutinin (HA) protein from an HPAI virus induce high-titer broadly neutralizing (cross-clade) antibodies in both mice and non-human primates. They also protect against lethal AIV infection. The goal of the current project is to further develop and test novel, optimized, VSV-based AIV vaccine vectors that produce much higher levels of the AIV HA. These vectors should also induce much higher neutralizing antibody titers and are expected to generate maximal cross-clade neutralizing antibody titers to AIVs. The optimized, highly attenuated or replication-defective, single-cycle VSV vectors to be developed could form the basis for a broadly protective AIV vaccine that could be produced and deployed rapidly in response to an influenza virus pandemic. PUBLIC HEALTH RELEVANCE: Influenza pandemics in the 20th century are estimated to have killed more than 40 million people worldwide. Future pandemics will surely occur and are highly likely to result from mutation of avian influenza virus and crossover into the human population. The goal of this project is to develop a novel type of vaccine that elicits very broad neutralizing antibody and broad protection against avian influenza virus strains. In addition, unlike traditional influenza vaccines, this vaccine could be produced and deployed rapidly to halt a pandemic.

描述（由申请人提供）：高致病性禽流感（HPAI）病毒可能在未来某个时候引起流感大流行。传统的流感疫苗生产方法可能太慢，无法有效应对这种大流行。因此，开发能够预防此类大流行的快速部署疫苗平台至关重要。基于重组活、减毒或复制缺陷型水泡性口炎病毒（VSV）的疫苗载体是迄今为止测试的最有效的疫苗载体之一。它们还有一个主要优势，即人群中不存在针对该载体的免疫力。表达来自 HPAI 病毒的 H5N1 血凝素 (HA) 蛋白的 VSV 载体在小鼠和非人灵长类动物中诱导高滴度广泛中和（跨进化枝）抗体。它们还可以防止致命的 AIV 感染。当前项目的目标是进一步开发和测试新型、优化的、基于 VSV 的 AIV 疫苗载体，以产生更高水平的 AIV HA。这些载体还应诱导更高的中和抗体滴度，并有望产生针对 AIV 的最大跨进化枝中和抗体滴度。待开发的优化、高度减毒或复制缺陷型单周期 VSV 载体可以构成广泛保护性 AIV 疫苗的基础，该疫苗可以快速生产和部署，以应对流感病毒大流行。公共卫生相关性：据估计，20 世纪的流感大流行已导致全球超过 4000 万人死亡。未来的大流行肯定会发生，并且很可能是由于禽流感病毒突变并交叉传播到人群中造成的。该项目的目标是开发一种新型疫苗，可引发非常广泛的中和抗体并对禽流感病毒株提供广泛的保护。此外，与传统流感疫苗不同，这种疫苗可以快速生产和部署以阻止大流行。