权益分类	功能权益	普通用户	{{item.name}}会员
{{category.name}}	{{benefitItem.name}}

HMGB1-Derived Peptides As Vaccine Adjuvants

HMGB1 衍生肽作为疫苗佐剂

基本信息

批准号：
8435590
负责人：
BRADLEY T MESSMER
金额：
$ 29.06万
依托单位：
UNIVERSITY OF CALIFORNIA, SAN DIEGO
依托单位国家：
美国
项目类别：
财政年份：
2012
资助国家：
美国
起止时间：
2012-04-15 至 2014-03-31
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/8435590
关键词：
Acute Acute Disease Adjuvant Affinity Alanine Aluminum Compounds Amino Acid Motifs Amino Acids Animals Anogenital region Antibodies Antibody Formation Antigens Autoimmunity Binding Biological Assay Blinded CD8B1 gene Cavia Cells Clinical DNA Data Dendritic Cells Dendritic cell activation Development Disease Dose Drug Formulations Encapsulated FDA approved Family Future Genital system Glycolates Goals HMGB Proteins HMGB1 Protein Harvest Human Human Herpesvirus 2 Immune response Immune system Immunity Immunization In Vitro Infection Knowledge Measures Memory Modeling Molecular Mus Names Necrosis Organ Ovalbumin Pattern Peptides Plaque Assay Play Preparation Production Property Proteins Recurrence Recurrent disease Role Safety Simplexvirus Spinal Ganglia Stimulus Structure Surface Plasmon Resonance Swab T cell response T-Lymphocyte Testing Therapeutic Time Tissues Toxic effect Vaccination Vaccine Adjuvant Vaccines Vagina Viral Viral Load result Virus Virus Replication Virus Shedding Work acquired immunity adaptive immunity aluminum sulfate base cell mediated immune response clinically relevant cost cytokine dimer glycoprotein D-herpes simplex virus type 2 in vivo infectious disease treatment monomer mouse model nanoparticle novel novel vaccines prophylactic protective efficacy receptor research study

项目摘要

DESCRIPTION (provided by applicant): Currently, aluminum compounds and more recently MPL are the only adjuvants approved by the FDA for use in humans in the U.S. Because of its ineffectiveness for some antigens and inability to augment cell mediated immune responses, there is still a need to discover new, more potent, and safer adjuvants for human vaccination. Dendritic cells play a central role in guiding the development of adaptive immunity. Due to their intrinsic properties, harnessing dendritic cells for vaccination will likely result in a more robust immune response. We have demonstrated that high mobility group box protein 1 (HMGB1) and its fragments can act as potent maturation stimuli for human and mouse dendritic cells and are therefore promising candidates for adjuvants. The overall goal of this project is to investigate the efficacy of and develop the HMGB1-derived peptide Hp91 as vaccine adjuvant for herpes simplex virus 2 infections in mouse and guinea pig models. In Aim 1 we will assess the efficacy of the Hp91 adjuvant in combination with 3 HSV-2 antigens for protection against virus challenge and identify the most potent peptide format and formulation. In Aim 2 we will determine to what extent the most potent vaccine format provides HSV-2 protection in the guinea pig model that mimics human genital disease. In Aim 3 we will evaluate the safety profile of the vaccine. In Aim 4 we will determine the mechanism by which the peptide induces immune responses. We will perform structure function studies to determine critical amino acids and investigate receptor involvement. Overall these studies will determine to what extent the HMGB1-derived peptide Hp91 act as adjuvants in eliciting protective immune responses to HSV-2. These studies will provide the basis for testing its broad applicability to other clinically relevant antigens.

描述（由申请人提供）：目前，铝化合物和最近的MPL是美国FDA批准用于人类的唯一佐剂。由于其对某些抗原无效，不能增强细胞介导的免疫反应，仍然需要发现新的，更有效的，更安全的人疫苗佐剂。树突状细胞在引导适应性免疫的发展中起着核心作用。由于它们的内在特性，利用树突状细胞进行疫苗接种可能会产生更强大的免疫反应。我们已经证明，高迁移率组盒蛋白1 （HMGB1）及其片段可以作为人类和小鼠树突状细胞的有效成熟刺激，因此是有希望的佐剂候选人。本项目的总体目标是在小鼠和豚鼠模型上研究和开发hmgb1衍生肽Hp91作为单纯疱疹病毒2型感染的疫苗佐剂的功效。在目标1中，我们将评估Hp91佐剂与3种HSV-2抗原联合抵抗病毒攻击的功效，并确定最有效的肽格式和配方。在目标2中，我们将确定最有效的疫苗格式在模仿人类生殖器疾病的豚鼠模型中提供HSV-2保护的程度。在目标3中，我们将评估疫苗的安全性。在Aim 4中，我们将确定肽诱导免疫反应的机制。我们将进行结构功能研究，以确定关键氨基酸和调查受体参与。总的来说，这些研究将确定hmgb1衍生的肽Hp91在多大程度上作为佐剂，引发对HSV-2的保护性免疫反应。这些研究将为测试其对其他临床相关抗原的广泛适用性提供基础。