Novel vaccine to enhance breadth of influenza immunity by skin vaccination

通过皮肤疫苗接种增强流感免疫力的新型疫苗

• 批准号: 9125732
• 负责人: Baozhong Wang
• 金额: $ 60.67万
• 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: 2015-08-12 至 2019-07-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/9125732
• 关键词: Adjuvant; Aerosols; Animal Model; Antigens; Body Weight decreased; Cavia; Chimeric Proteins; Clinical Trials; Data; Effectiveness; Encapsulated; Evaluation; Ferrets; Flagellin; Genes; Genetic; Goals; Health; Human; Immune; Immune response; Immunity; Immunization; Infection; Influenza; Influenza A virus; Intramuscular; Intramuscular Injections; Ligands; Modeling; Mus; Nose; Point Mutation; Polymers; Predisposition; Prevention; Property; Proteins; Public Health; Readiness; Reporting; Signal Pathway; Skin; TLR5 gene; Tandem Repeat Sequences; Testing; Update; Vaccinated; Vaccination; Vaccines; Variant; Viral; Virus; Virus Shedding; base; biocompatible polymer; design; disorder prevention; efficacy testing; flu transmission; human data; improved; influenza virus vaccine; influenzavirus; innovation; nonhuman primate; novel strategies; novel vaccines; pandemic disease; pandemic influenza; prevent; protective efficacy; seasonal influenza; success; transmission process; vaccine candidate

 DESCRIPTION (provided by applicant): Influenza is a worldwide public health problem. The present seasonal vaccines are effective in prevention of disease induced by closely matched viruses. However, because of the continuous accumulation of point mutations, genetic reassortment between different subtypes, and non-human influenza virus adaption to humans, mismatch between vaccines and circulating viruses compromises the efficacy of current vaccines and results in increased susceptibility of vaccinated subjects. New vaccine strategies capable to provide enhanced protection by seasonal vaccines against heterologous viruses will have an important impact on public health. We recently reported that microneedle-based skin vaccination with a fusion protein including M2e tandem repeats and the Toll-like receptor (TLR) 5 ligand from bacterial flagellin (4.M2e-tFliC) elicited effective protection against heterosubtypi viruses. We will investigate whether a boost immunization with dissolving polymer microneedles patch delivering redesigned 4.M2e-tFliC to skin after the conventional vaccination, or a microneedle patch co- delivering conventional vaccines and 4.M2e-tFliC, will rapidly broaden the protective efficacy of current seasonal vaccines against an emerging drift variant or even a potential pandemic strain. We will pursue two specific aims: Specific Aim 1. Evaluation of enhanced immune protection against drifted viruses as well as potential pandemic strains in mice. We will test whether a boost immunization with dissolving microneedles delivering 4.M2e-tFliC to skin after conventional immunization, or microneedle co-delivery of split vaccines and 4.M2e-tFliC, will elicit enhanced protection against an emerging drift or potential pandemic variant. Specific Aim 2. Determination of enhanced protection in guinea pigs. As a more relevant animal model to obtain proof-of-concept data for human skin vaccination and prevention of influenza transmission, we will determine: 1) whether a boost immunization with 4.M2e-tFliC-encapsulated dissolving microneedles after conventional vaccination, or microneedles co-delivering split vaccines plus 4.M2e-tFliC to skin, will induce enhanced immune responses conferring protection against heterologous viruses in guinea pigs; and 2) whether the proposed vaccine strategies will prevent contact and aerosol transmission from infected guinea pigs as a donor to mimic natural infection. Overall, our approach is innovative in combining 4.M2e-tFliC encapsulated in dissolving microneedle patches with conventional influenza vaccines, and will provide a promising novel approach to provide additional protection to vaccines when a new drift or pandemic strain is emerging.

 描述（由适用提供）：流感是全球公共卫生问题。当前的季节性疫苗可有效预防由密切相匹配的病毒引起的疾病。然而，由于点突变的连续积累，不同亚型之间的遗传缓解以及非人类影响病毒对人类的适应性，疫苗和循环病毒之间的不匹配损害了当前疫苗的有效性，并导致疫苗接种受试者的易感性增加。新的疫苗策略可以通过季节性疫苗对异源病毒提供增强的保护，将对公共卫生产生重要影响。我们最近报道说，基于微针的皮肤，具有融合蛋白（包括M2E串联重复序列）和Toll样受体（TLR）5配体的融合蛋白吸尘，来自细菌鞭毛蛋白（4.M2E-TFLIC）具有有效保护的有效保护，以防止异性杀伤性病毒。 We We will investigate whether a boost immunosuppression with dissolving polymer microneedles patch delivering redesigned 4.M2e-tFliC to skin after the conventional vaccine, or a microneedle patch co-delivering conventional vaccines and 4.M2e-tFliC, will rapidly broaden the protective efficiency of current seasonal vaccines against an emerging drift variant or even a potential pandemic strain.我们将追求两个具体目标：特定目标1。评估增强的免疫抑制保护针对漂移病毒的保护以及小鼠中潜在的大流行菌株。我们将测试传统免疫抑制后溶解4.m2e-tflic的微针的增强免疫抑制，还是分裂疫苗和4.M2E-TFLIC的微针共递送，将增强对新兴漂移或潜在的PANDEACTIAM变量的保护。具体目标2。确定豚鼠的保护增强。作为一个更相关的动物模型，以获取人类皮肤疫苗的概念证明数据和预防影响力的传播，我们将确定：1）通过4.m2e-tflic-tflic-apapsaps溶解的微孔疫苗溶解的微针的促进免疫抑制是在传统的疫苗后溶解的，或者是在传统的疫苗后溶解的，或者是在传统的疫苗中降低了分裂疫苗的影响。豚鼠； 2）提出的疫苗策略是否会防止接触和被感染的豚鼠的气溶胶传播，作为模仿自然感染的供体。总体而言，我们的方法在结合4.m2e-tflic中具有创新性，这些4.m2e-tflic封装在将微针斑块与常规影响疫苗中溶解，并将在新的漂移或大流行菌株出现时提供有望的新方法，为疫苗提供额外的保护。