VLP-based Vaccines for Targeting Staphylococcus aureus Secreted Virulence Factors

针对金黄色葡萄球菌分泌毒力因子的 VLP 疫苗

基本信息

批准号：
8967305
负责人：
Pamela Ranel Hall
金额：
$ 22.65万
依托单位：
UNIVERSITY OF NEW MEXICO HEALTH SCIS CTR
依托单位国家：
美国
项目类别：
财政年份：
2015
资助国家：
美国
起止时间：
2015-07-01 至 2017-06-30
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/8967305
关键词：
Abscess Accident and Emergency department Address Adjuvant Affinity Amino Acid Sequence Animal Model Antibiotic Resistance Antibodies Antigens Area Autoantigens Bacteremia Bacterial Infections Binding Blood Cells Chemical Agents Control Groups Cytolysis Data Development Disease Effectiveness Epitopes FDA approved Failure Goals Hemolysin Human Human Papilloma Virus Vaccine Immune Immune Sera Immune Tolerance Immune response Immunity Immunoglobulin G In Vitro Individual Infection Infectious Skin Diseases Knowledge Modeling Morbidity - disease rate Mus Necrosis Panton-Valentine leukocidin Pathogenesis Peptide Library Peptides Phase III Clinical Trials Serum Skin Tissue Soft Tissue Infections Staphylococcus aureus Stream Structure Targeted Toxins Testing Toxin Translating Vaccinated Vaccination Vaccine Design Vaccine Production Vaccines Virulence Virulence Factors Virus-like particle Work adaptive immunity base commensal microbes cytokine design flexibility immunogenicity innovation killings leukotoxin methicillin resistant Staphylococcus aureus mortality novel novel strategies pathogen peptide based vaccine prevent public health relevance screening subcutaneous vaccine efficacy ventilator-associated pneumonia

项目摘要

DESCRIPTION (provided by applicant): To date, no vaccine to prevent Staphylococcus aureus infection has succeeded in Phase III clinical trials. Meanwhile, the need for a vaccine continues to escalate as does the ability of this pathogen to acquire antibiotic resistance. Our goal is to demonstrate the effectiveness of virus-like particles (VLPs) as an innovative broad- spectrum platform for production of vaccines against S. aureus secreted virulence factors. VLPs are a novel approach to the design of vaccines targeting bacterial infection and the ability of VLP-based vaccines targeting secreted S. aureus toxins to induce a protective immune response has not been investigated. Therefore, the goal of this proposal is to test the hypothesis that presentation of toxin peptides on VLPs can be used to induce adaptive immunity targeting major S. aureus secreted virulence factors. To test this hypothesis we will pursue the following specific aims: Specific Aim #1: To determine the immunogenicity and efficacy of VLPs displaying structurally selected Hla and bi-component leukotoxin peptides in naïve and S. aureus colonized mice. Specific Aim #2: To determine the immunogenicity and efficacy of VLPs displaying 10-mer peptides representing the toxin peptidome of Hla and bi-component leukotoxins in naïve and S. aureus colonized mice. Importantly, unlike other platforms and experimental adjuvants, VLPs are currently used in FDA-approved vaccines (like the current HPV vaccines). Therefore, if experimental approaches using VLPs are confirmed in animal models, they can potentially translate into human trials fairly readily.

描述（由申请人提供）：迄今为止，还没有预防金黄色葡萄球菌感染的疫苗在临床试验中取得成功，同时，对疫苗的需求不断增加，这种病原体获得抗生素耐药性的能力也在不断增加。证明病毒样颗粒（VLP）作为生产针对金黄色葡萄球菌分泌毒力因子的疫苗的创新广谱平台的有效性，VLP是设计针对细菌感染和细菌感染的疫苗的一种新方法。基于 VLP 的疫苗靶向分泌的金黄色葡萄球菌毒素诱导保护性免疫反应的能力尚未得到研究。因此，本提案的目的是检验 VLP 上毒素肽的呈现可用于诱导适应性免疫靶向的假设。为了检验这一假设，我们将追求以下具体目标：具体目标#1：确定展示结构选择的 Hla 和双组分的 VLP 的免疫原性和功效。特定目标#2：确定展示代表 Hla 毒素肽组和双组分白细胞毒素的 10 聚体肽的 VLP 在幼稚小鼠和金黄色葡萄球菌定植小鼠中的免疫原性和功效。与其他平台和实验佐剂不同，VLP目前用于FDA批准的疫苗中（如目前的HPV因此，如果使用 VLP 的实验方法在动物模型中得到证实，它们可能很容易转化为人体试验。