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High-density flagellin-displayed virus-like particle for universal influenza vaccine development'

用于通用流感疫苗开发的高密度鞭毛蛋白展示病毒样颗粒

基本信息

批准号：
10302484
负责人：
Xinyuan Chen
金额：
$ 19.69万
依托单位：
UNIVERSITY OF RHODE ISLAND
依托单位国家：
美国
项目类别：
财政年份：
2021
资助国家：
美国
起止时间：
2021-06-11 至 2023-05-31
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/10302484
关键词：
Adjuvant Adverse reactions Affect Agonist Animal Model Antibodies Antibody titer measurement Body Weight decreased Cell Maturation Clinical Clinical Research Clinical Trials Cytotoxic T-Lymphocytes Dendritic Cells Development Dose Encapsulated Epitopes Flagellin Head Hemagglutinin Hepatitis B Human Immune response Immunity Influenza A Virus, H1N1 Subtype Influenza A Virus, H3N2 Subtype Influenza A virus Length Lung Morphology Mus National Institute of Allergy and Infectious Disease Natural Immunity Nucleoproteins Production Proteins Recombinant Vaccines Recombinants Research Risk Role Safety Surface TLR5 gene Testing Time Vaccine Antigen Vaccines Viral Virus-like particle antiviral immunity base cross reactivity density extracellular immunogenic immunogenicity improved influenza virus vaccine mouse model neutralizing antibody nicotine vaccine nonhuman primate novel virus pre-clinical preclinical evaluation preclinical study protective efficacy response self assembly universal influenza vaccine vaccine development virus core

项目摘要

Project Summary/Abstract Current influenza vaccines mainly induce strain-specific protection. Universal influenza vaccines are under active development to induce broad cross-protection. Extracellular ectodomain of matrix protein 2 (M2e) and intracellular nucleoprotein (NP) are highly conserved across viral strains and are attractive targets in universal influenza vaccine development. Various preclinical and clinical studies support the induction of anti-M2e antibodies and anti-NP cytotoxic T lymphocytes (CTLs) to induce broad cross-protective immunity. Due to the low immunogenicity of M2e and NP, highly immunogenic vaccine carriers are demanded to present these conserved vaccine antigens to induce potent cross-reactive immune responses. This proposal explores our recently developed high-density flagellin-displayed hepatitis b core (HBc) virus-like particles (VLPs) (FH VLPs) in combination with a clinical CpG adjuvant (FHc VLPs) for universal influenza vaccine development. FH VLPs show better immunogenicity and safety than FljB and more versatility than HBc VLPs for vaccine development. Furthermore, a clinical CpG adjuvant will be encapsulated into the core of FH VLPs to potentiate vaccine- induced humoral immune responses and at the same time to induce potent CTL responses. This proposal prepares M2e and NP-displayed FHc VLP-based universal influenza vaccines (Specific aim 1) and explore their safety, immunogenicity, and cross-protective efficacy in murine models (Specific aim 2). This proposal is in response to National Institute of Allergy and Infectious Diseases (NIAID)'s call for Advancing Research Needed to Develop a Universal Influenza Vaccine (PA-18-858).

项目总结/文摘