LAIV Inducing Cross Protection

LAIV 诱导交叉保护

• 批准号: 8951382
• 负责人: SANG-MOO KANG
• 金额: $ 18.76万
• 依托单位: GEORGIA STATE UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2015
• 资助国家: 美国
• 起止时间: 2015-05-01 至 2017-04-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8951382
• 关键词: 2 year old; Adult; Animal Model; Antibodies; Antibody Response; Attenuated; Attenuated Vaccines; Child; Development; Epidemic; Epitopes; Ferrets; Figs - dietary; Genes; Goals; Head; Hemagglutinin; Human; Immune response; Immunity; Inactivated Vaccines; Influenza; Influenza A Virus, H1N1 Subtype; Influenza A Virus, H5N1 Subtype; Influenza A virus; Influenza vaccination; Licensing; Life; M2 protein; Mus; Mutation; Phenotype; Polymerase; Proteins; Public Health; Recombinants; Safety; Site; Supplementation; Tandem Repeat Sequences; Testing; Vaccinated; Vaccines; Variant; Vertebral column; Virus; attenuation; base; immunogenic; immunogenicity; improved; influenza virus vaccine; influenzavirus; mutant; novel; novel strategies; pandemic disease; protective efficacy; public health relevance; recombinant virus; vaccine trial; vector vaccine

 DESCRIPTION (provided by applicant): Live attenuated influenza vaccine (LAIV) is a safe and effective platform for human use, and shown to have higher efficacy in children than inactivated vaccine. Nonetheless, current influenza vaccines including LAIV do not provide cross-protection against antigenically distinct epidemic strains or the unanticipated emergence of new pandemic strains. It is of a high priority to improve the breadth of cross protective efficacy of strain-specific vaccines based on hemagglutinin (HA) immunity. Our preliminary studies demonstrated that immune responses to highly conserved influenza M2 protein (M2e) provided a broader range of cross-protection (H1, H3, and H5 subtypes). In addition, we recently generated novel influenza mutants that express a chimeric conserved M2e-HA, which showed attenuated phenotypes as well as provided significantly broad and enhanced cross-protection. These findings strongly suggest that it should be possible to produce highly cross protective and safe LAIV. Thus, it is highly expected that incorporating conserved-protective M2e into HA will overcome the strain-specific protection of HA as well as poor immunogenicity of M2. The central hypothesis is that recombinant LAIV containing M2e-HA will be safer and more effective in inducing a broader range of cross-protection. The first goal (aim 1) is to generate recombinant LAIV containing M2e-HA and to determine the safety and cross-protective efficacy of recombinant LAIV. The aim 2 will test recombinant LAIV-M2e vaccines in ferrets, which is a more relevant animal model for testing influenza vaccines.

 描述（由申请人提供）：减毒流感疫苗（LAIV）是一种安全有效的人类使用平台，在儿童中比灭活疫苗具有更高的功效，但是，包括 LAIV 在内的现有流感疫苗不能提供交叉保护。抗原不同的流行毒株或新的流行毒株的意外出现，提高基于血凝素（HA）免疫的毒株特异性疫苗的交叉保护效力的广度是当务之急。对高度保守的流感 M2 蛋白 (M2e) 的免疫反应提供了更广泛的交叉保护（H1、H3 和 H5 亚型）。此外，我们最近生成了表达嵌合保守 M2e-HA 的新型流感突变体，该突变体表现出减毒作用。表型并提供显着广泛和增强的交叉保护，这些发现强烈表明应该有可能产生高度交叉保护和安全的 LAIV，因此，人们高度期望掺入保守保护性 M2e。将HA转化为HA将克服HA的毒株特异性保护以及M2的较差免疫原性。第一个目标是含有M2e-HA的重组LAIV将更安全、更有效地诱导更广泛的交叉保护。目标1)是产生含有M2e-HA的重组LAIV并确定重组LAIV的安全性和交叉保护功效。目标2将测试重组LAIV-M2e。雪貂疫苗是测试流感疫苗更相关的动物模型。