New Vaccine against Influenza

新型流感疫苗

基本信息

批准号：
7929638
负责人：
MINGTAO ZENG
金额：
$ 36.75万
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 2012-08-31
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/7929638
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 Weight Body Weight Changes Body Weight decreased Cells Cellular Immunity Chimeric Proteins Clinical Code Codon Nucleotides Communicable Diseases Computer Systems Development Containment Cytotoxic T-Lymphocytes Data Development Disease Outbreaks Edema Enzyme-Linked Immunosorbent Assay Escherichia coli Europe Evaluation Ferrets Fusion Protein Expression Fusion Toxin Genes Hand Histopathology Human Human Virus 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 Temperature 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 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（由申请人提供）：流感是主要的公共卫生威胁和NIH Biodefense研究的重点之一。 H5N1流感病毒从鸟类传播到人类，表现出非常紧迫的抗流感疫苗。这项研究的目的是使用H5N1禽流感病毒的相对保守的基质蛋白2（M2）开发有效的流感疫苗，作为由排毒的炭疽性水肿毒素传递的抗原。由于炭疽毒素能够通过主要的组织相容性复合物（MHC）和II类途径进入宿主细胞进行抗原递送，因此提出的疫苗可能会引起对流感抗原的有效细胞介导的免疫。我们假设所提出的疫苗能够针对H5N1和其他类型的流感病毒交叉保护。重要的是，拟议的疫苗可以通过非侵入性鼻粘膜途径进行管理，该鼻粘膜途径很方便，并且可能更有效地引起粘膜免疫，以防止可能的流血流感。为了评估这些假设，我们将评估拟议疫苗在小鼠模型中鼻内递送的疗效。该项目的具体目的是：特定目的＃1：用M2产生重组融合n-fifusion n-fragment。具体目的＃2：研究在小鼠中鼻内疫苗接种后与融合EFN/M2结合炭疽保护抗原的全身性和粘膜免疫。特定目的＃3：确定所提出的疫苗在小鼠模型中保护H5和其他流感A病毒菌株的疗效。特定目的＃4：评估疫苗接种后所提出的疫苗的毒性。拟议的研究的成功不仅将提供一种新的且易于给药的流感疫苗，还将提供针对其他传染病开发粘膜疫苗的平台。公共卫生相关性：流感既是主要的公共卫生威胁，又是NIAID生物融合研究的优先事项。 H5N1流感病毒从鸟类传播到人类，表现出对针对流感病毒的有效疫苗开发的迫切紧迫性。我们建议开发一种可以通过非侵入性鼻粘膜途径进行管理的疫苗，并可能更有效地引起粘膜和系统性免疫，以防止可能的流血流感。这将满足公共卫生的迫切需求。