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Novel VLP vaccines for pandemic influenza virus

针对大流行性流感病毒的新型 VLP 疫苗

基本信息

批准号：
7914758
负责人：
RICHARD W COMPANS
金额：
$ 16.29万
依托单位：
EMORY UNIVERSITY
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：
2009-09-12 至 2011-08-31
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/7914758
关键词：
Address Amantadine Antibodies Antigen Targeting Antigen-Presenting Cells Antigens Antiviral Agents Avian Influenza A Virus B-Lymphocytes Baculovirus Expression System Baculoviruses Binding Biological Assay Biological Models Birds Bone Marrow CD4 Positive T Lymphocytes CTL assay Cell surface Cells Chickens Core Protein Country Ensure Enzymes Epitopes Event Exhibits Formalin Galactosidase Glycoproteins Goals Granulocyte-Macrophage Colony-Stimulating Factor H5 hemagglutinin Hemagglutination Hemagglutinin Home environment Human Immune response Immunity Immunization Infection Influenza Influenza A Virus, H1N1 Subtype Influenza A Virus, H5N1 Subtype Influenza Hemagglutinin Institute of Medicine (U.S.)Label Langerhans cell Life Ligands Lung Lymphoid Measures Mediating Membrane Memory Memory B-Lymphocyte Methods Modeling Monitor Morbidity - disease rate Mus Neuraminidase Organ Peptides Phenotype Plasma Cells Population Production Property Proteins Readiness Recombinants Recurrence Research Personnel Resistance Rimantadine Serotyping Source Southeastern Asia Staining method Stains Surface T-Lymphocyte Testing Tissues Transgenic Mice Vaccination Vaccine Production Vaccines Viral Viral Hemagglutinins Virus Virus Diseases Virus-like particle aquatic bird base cell mediated immune response cost cytokine design efficacy testing egg enzyme linked immunospot assay experience expression vector glycosylation immunogenic immunogenicity in vivo influenza epidemic influenza virus vaccine influenzavirus macrophage mortality mouse model neutralizing antibody novel novel vaccines novel virus pandemic disease pandemic influenza programs protective efficacy response vaccine candidate vaccine efficacy

项目摘要

A large spectrum of avian influenza virus to which the human population is naTve is present in wild aquatic birds, and highly pathogenic H5N1 avian strains are currently circulating in several countries in southeast Asia where they have caused dozens of human fatalities. These strains are of particular concern because they are resistant to the most cost-effective antiviral drugs, amantadine and rimantadine. The emergence of a novel transmissible influenza virus against which the population has little or no immunity would cause a global pandemic, for which no vaccine is available. Current influenza vaccines are produced from viruses that are adapted to grow well in embryonated hens' eggs, whereas highly pathogenic avian influenza viruses are lethal for hens' eggs, making the current methods of vaccine production problematic. Alternative approaches to develop effective influenza vaccines are therefore urgently needed. In an effort to develop alternatives for influenza vaccine production and in response to a pandemic threat, our goal in this project is to determine whether influenza virus-like particle based vaccines will provide protective immunity against a highly pathogenic avian influenza virus. Additional goals are to address other shortcomings of current influenza vaccines: they exhibit limited efficacy, they fail to protect against infection at mucosal surfaces, and the observed immunity is highly strain-specific and of short duration. Thus, we will develop approaches to enhance the immunogenicity of influenza vaccines, to enhance memory responses to the vaccine, and to induce effective immune responses at mucosal surfaces which may be protective against a broader range of viral strains. In addition to a panel of assays to monitor humoral and cellular immune responses, we will make use of novel transgenic mice which have been constructed to directly measure the magnitude of B cell memory generated in response to immunization. The specific aims of the project are:1. to produce virus-like particles (VLPs) incorporating influenza viral glycoproteins and matrix (M1) protein; 2. to characterize humoral and cellular immune responses after immunization with influenza VLPs and their protective efficacy; and 3. to develop more effective influenza VLP-based vaccines by incorporation of ligands designed to target the VLPs to antigen-presenting cells.

在野生水生动物中存在大量人类原生感染的禽流感病毒