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New Vaccine against Influenza

新型流感疫苗

基本信息

批准号：
8146178
负责人：
MINGTAO ZENG
金额：
$ 36.39万
依托单位：
TEXAS TECH UNIVERSITY HEALTH SCIS CENTER
依托单位国家：
美国
项目类别：
财政年份：
2009
资助国家：
美国
起止时间：
2009-09-11 至 2014-08-31
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/8146178
关键词：
Amino Acids Animals Anthrax disease Antibody Formation Antigen Presentation Antigens Asia Autopsy Avian Influenza A Virus Binding Biological Assay Birds Blood Chemical Analysis Body Temperature Body Weight Body Weight Changes Body Weight decreased Cells Cellular Immunity Chimeric Proteins Clinical Code Codon Nucleotides Communicable Diseases Containment Cytotoxic T-Lymphocytes Data Development Disease Outbreaks Edema Enzyme-Linked Immunosorbent Assay Escherichia coli Europe Evaluation Ferrets Fusion Protein Expression Fusion Toxin Genes Health His-His-His-His-His-His Histopathology Human Human Virus Humoral Immunities Immune Sera Immune response Immunity Immunization Immunization Schedule Inbred BALB C Mice Influenza Influenza A Virus, H1N1 Subtype Influenza A Virus, H5N1 Subtype Influenza A virus Life Lung Major Histocompatibility Complex Measures Mediating Metabolic Clearance Rate Methods Monitor Mucosal Immunity Mus National Institute of Allergy and Infectious Disease Neurologic Nose Organ Weight Pathway interactions Property Proteins Protocols documentation Public Health Recombinants Research Research Priority Route Safety Serum Staining method Stains Survival Rate System Systems Development Testing Thailand Toxic effect Toxin United States National Institutes of Health Vaccinated Vaccination Vaccine Research Vaccines Vietnam Virus Virus Diseases anthrax edema factor anthrax lethal factor anthrax protective factor anthrax toxin base biodefense cell mediated immune response cytokine design experience expression vector food consumption gene synthesis immunogenicity influenza virus vaccine influenzavirus meetings mortality mouse model mucosal vaccine neutralizing antibody novel vaccines pandemic disease pandemic influenza positional cloning protective efficacy public health relevance research study response success technology development transmission process trioctyl phosphine oxide vaccine development vaccine efficacy

项目摘要

DESCRIPTION (provided by applicant): Influenza is one of the major public health threats and NIH biodefense research priorities. Transmission of H5N1 influenza virus from the avian species to human shows great urgency for the development of an effective vaccine against influenza. The objective of this research is to develop an effective influenza vaccine using the relatively conserved matrix protein 2 (M2) of H5N1 avian influenza A virus as an antigen delivered by a detoxified anthrax edema toxin. Since the anthrax toxins are capable of entering host cells for antigen delivery through the major histocompatibility complex (MHC) class I and class II pathways, the proposed vaccine may elicit potent cell-mediated immunity against influenza antigens. We hypothesize that the proposed vaccine is able to cross-protect against H5N1 and other types of influenza A viruses. Importantly, the proposed vaccine could be administrated through a noninvasive nasal mucosal route which is convenient for administration and maybe more efficient to elicit mucosal immunity for protection against a possible pandemic influenza. In order to evaluate these hypotheses, we will evaluate the efficacy of intranasal delivery of the proposed vaccine in a mouse model. The specific aims of this project are: Specific Aim #1: To produce recombinant fusion N-fragment of anthrax edema factor with M2. Specific Aim #2: To study the systemic and mucosal immunity against influenza viruses after intranasal vaccination in mice with the fusion EFn/M2 in combination with the anthrax protective antigen. Specific Aim #3: To determine the efficacy of the proposed vaccine for protection against H5 and other influenza A virus strains in a mouse model. Specific Aim #4: To assess toxicity of the proposed vaccine in animals after vaccination. The success of the proposed research will provide not only a new and easily administered influenza vaccine but also a platform for development of mucosal vaccines against other infectious diseases. PUBLIC HEALTH RELEVANCE: Influenza is both a major public health threat and a NIAID biodefense research priority. Transmission of H5N1 influenza virus from the avian species to human shows great urgency for the development of an effective vaccine against influenza viruses. We propose to develop a vaccine which could be administrated through a noninvasive nasal mucosal route and maybe more efficient to elicit mucosal and systemic immunity for protection against a possible pandemic influenza. This will meet the urgent need for public health.

描述(由申请者提供)：流感是主要的公共卫生威胁之一，也是NIH生物防御研究的重点。H5N1流感病毒从禽类向人类的传播表明，开发有效的流感疫苗非常紧迫。本研究的目的是利用H5N1禽流感病毒相对保守的基质蛋白2(M2)作为解毒炭疽水肿素递送的抗原，研制出一种有效的流感疫苗。由于炭疽毒素能够通过主要组织相容性复合体(MHC)I类和II类途径进入宿主细胞进行抗原传递，因此拟议的疫苗可能会诱导针对流感抗原的强大细胞免疫。我们假设建议的疫苗能够对H5N1和其他类型的甲型流感病毒产生交叉保护作用。重要的是，建议的疫苗可以通过一种非侵入性的鼻黏膜途径接种，这种途径给药方便，可能更有效地诱导粘膜免疫，以预防可能的大流行流感。为了评估这些假说，我们将在小鼠模型中评估所建议的疫苗鼻腔给药的有效性。本项目的具体目标是：具体目标1：制备炭疽水肿因子与M2的重组融合N-片段。特定目的#2：研究融合EFN/M2与炭疽保护性抗原联合鼻腔免疫小鼠后对流感病毒的系统免疫和粘膜免疫。具体目标#3：在小鼠模型中确定所建议的疫苗对H5和其他甲型流感病毒株的保护效果。具体目标#4：评估疫苗接种后对动物的毒性。拟议研究的成功不仅将提供一种新的、易于管理的流感疫苗，而且还将为开发针对其他传染病的粘膜疫苗提供一个平台。公共卫生相关性：流感既是一个主要的公共健康威胁，也是NIAID生物防御研究的优先事项。H5N1流感病毒从禽类向人类的传播表明，迫切需要开发有效的流感病毒疫苗。我们建议开发一种疫苗，这种疫苗可以通过非侵入性的鼻黏膜途径给药，并且可能更有效地诱导粘膜和系统免疫，以预防可能的大流行流感。这将满足公共卫生的迫切需要。