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（由适用提供）：活衰减影响疫苗（LAIV）是人类使用的安全有效平台，与灭活疫苗相比，儿童对儿童的有效性更高。尽管如此，包括LAIV在内的当前影响疫苗并不能对抗原上不同的流行病或新大流行菌株的意外出现提供交叉保护。基于血凝集素（HA）免疫史的菌株特异性疫苗的疗效，提高交叉保护的宽度是一个很高的优先级。我们的初步研究表明，对高度组成影响的免疫反应（M2E）提供了更广泛的跨保护范围​​（H1，H3和H5亚型）。此外，我们最近产生了表达嵌合保守的M2E-HA的新型影响，该影响显示出衰减的表型，并提供了显着宽阔和增强的交叉保护。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。这是高度期望的，将成立的保护M2E纳入HA将克服对HA的应变特异性保护以及M2的免疫原性。中心假设是，含有M2E-HA的重组LAIV将在诱导更广泛的跨保护范围​​内更安全，更有效。第一个目标（AIM 1）是生成含有M2E-HA的重组LAIV，并确定重组LAIV的安全性和交叉保护效率。 AIM 2将测试雪貂中的重组LAIV-M2E疫苗，这是测试影响力疫苗的更相关的动物模型。