Optimization of VesiVax® Lipidated Tucaresol Formulations

VesiVax® 脂化 Tucaresol 配方的优化

基本信息

批准号：
9131908
负责人：
Gary Fujii
金额：
$ 22.5万
依托单位：
MOLECULAR EXPRESS, INC.
依托单位国家：
美国
项目类别：
财政年份：
2016
资助国家：
美国
起止时间：
2016-04-01 至 2018-03-31
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/9131908
关键词：
Adjuvant Agonist Aldehydes Animal Model Antigen Targeting Antigen-Presenting Cells Antigens Benzoic Acids Bioavailable Biological Assay California Characteristics Clinical DNA Data Development Digit structure Dinucleoside Phosphates Disease Dose Double-Stranded RNA Ensure Esters Female Formulation Genes Goals Human Human Herpesvirus 2 Immune Immune response Immunity Immunization Immunologic Adjuvants Inbred BALB C Mice Interferons Interleukin-2 Laboratories Lipid A Lipids Liposomes Lysine MAP Kinase Gene MAPK1 gene Modeling Molecular Monitor Oligonucleotides Peptide Vaccines Peptides Pharmaceutical Preparations Physiological Play Poly I-C Procedures Production Property Proteins Public Health RNA Recombinant Proteins Recombinants Reporting Research Research Institute Role Schiff Bases Signal Transduction Structure Subunit Vaccines Surface Surface Antigens System T-Cell Receptor T-Lymphocyte TLR3 gene TLR4 gene TLR7 gene Tail Technology Testing Toxic effect Universities Vaccination Vaccine Adjuvant Work antigen challenge base carbonyl group cost effective cytokine design interest meetings mouse model neutralizing antibody professor public health relevance receptor resiquimod response small molecule vaccine development

项目摘要

DESCRIPTION (provided by applicant): There is a significant interest and need for developing new immunostimulatory adjuvant molecules that stimulate potent immune responses. To date, the only immunostimulatory adjuvant molecule that has been approved for human use is the Toll-like Receptor (TLR) 4 agonist, monophosphoryl lipid A (MPL). Other immunostimulatory adjuvant molecules such as poly I:C, a synthetic double stranded RNA mimic (TLR3), resiquimod, a synthetic single stranded RNA mimic (TLR7/8) or CpG, a DNA oligonucleotide (TLR9), have been in clinical development for a number of disease indications. A new class of immunostimulatory adjuvant molecules, cyclic dinucleotides (CDNs), have recently been shown to exert potent immunostimulatory properties through activation of an internal receptor called the STimulator of INterferon Genes (STING). In this project, we propose to optimize a small molecule immunostimulatory adjuvant, tucaresol, which we have synthesized with a "lipid tail" to facilitate formulation in the VesiVax(r) vaccine and adjuvant platform technology. We will synthesize lipidated tucaresol (LT) derivatives and prepare VesiVax(r) LT formulations with a model recombinant protein antigen (i.e., gD3PEPcD-HD) which we have shown to provide protective immune responses in our well-characterized mouse model of intravaginal HSV2 challenge.

描述（由申请人提供）：人们对开发刺激有效免疫反应的新型免疫刺激佐剂分子有着浓厚的兴趣和需求，迄今为止，唯一已批准用于人类的免疫刺激佐剂分子是Toll样受体（TLR）。 4 激动剂，单磷酰脂质 A (MPL) 其他免疫刺激佐剂分子，例如聚 I:C，一种合成的双链 RNA 模拟物 (TLR3)，瑞西莫德是一种合成的单链 RNA 模拟物 (TLR7/8) 或 CpG，一种 DNA 寡核苷酸 (TLR9)，已针对多种疾病适应症进行临床开发。最近被证明可以通过激活称为干扰素基因 ST 刺激器 (STING) 的内部受体来发挥有效的免疫刺激特性。在这个项目中，我们建议优化一种小分子。免疫刺激佐剂妥卡雷索，我们用“脂质尾”合成，以促进 VesiVax(r) 疫苗和佐剂平台技术的配制。我们将合成脂化妥卡雷索 (LT) 衍生物，并用模型制备 VesiVax(r) LT 制剂。我们已证明重组蛋白抗原（即 gD3PEPcD-HD）可以在我们充分表征的阴道内小鼠模型中提供保护性免疫反应HSV2 挑战。