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VLP-based Vaccines for Targeting Staphylococcus Aureus β-barrel Toxins

基于 VLP 的针对金黄色葡萄球菌 β 桶毒素的疫苗

基本信息

批准号：
10538909
负责人：
Seth Michael Daly
金额：
$ 19.06万
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：
2022
资助国家：
美国
起止时间：
2022-07-20 至 2024-06-30
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/10538909
关键词：
Accident and Emergency department Address Affinity Alpha Particles Amino Acid Sequence Animals Antibiotic Resistance Antibiotics Antibodies Antibody Response Antigens Autoantigens Avidity Binding Blood Body Weight decreased Cells Chemical Agents Cytolysis Development Disease Epitopes Health Hemolysin Human Immune Immune Sera Immune Tolerance Immune response Immunity Immunoglobulin G In Vitro Individual Infection Infection prevention Infectious Skin Diseases Intramuscular Knowledge Lesion Mediating Methicillin Resistance Modeling Morbidity - disease rate Mus Panton-Valentine leukocidin Pathogenesis Patients Peptides Phase III Clinical Trials Publishing Serum Skin Tissue Soft Tissue Infections Staphylococcus aureus Staphylococcus aureus infection Stream Structure Tertiary Protein Structure Testing Toxin Vaccination Vaccine Research Vaccines Virulence Factors Virus-like particle Work adaptive immune response adaptive immunity base commensal bacteria design flexibility host colonization human disease human model human pathogen immune function immunogenicity improved in vivo leukotoxin methicillin resistant Staphylococcus aureus monomer mortality mouse model neutralizing antibody novel strategies pathogen patient population peptide based vaccine pre-clinical prevent recurrent infection vaccine development vaccine efficacy vaccine failure vaccine immunogenicity vaccine strategy ventilator-associated pneumonia virtual

项目摘要

PROJECT SUMMARY: Staphylococcus aureus (SA), including methicillin-resistant (MRSA), is the most common cause of skin and soft tissue infection (SSTI) in the US. SA causes recurrent infections, particularly in highly susceptible patient populations with reduced immune function. To date, no vaccine to prevent SA infection has succeeded in human trials. Meanwhile, the need for a vaccine continues to escalate, as does the ability of this pathogen to acquire antibiotic resistance. We have developed a virus-like particle (VLP)-based vaccine strategy to control SA secreted β-barrel pore-forming toxins. In models of skin infection, a vaccine based on this approach induces antibodies that prevent infection pathogenesis, spares host immune cells and limits disease. In this proposal, we aim to evaluate the preclinical potential of this vaccine strategy against a variety of SA β-barrel pore-forming toxins. We will determine vaccine immunogenicity in vivo, and efficacy in SA colonization. Our results could lay the groundwork for development of an efficacious vaccine to prevent SA infection and limit pathogenesis. This vaccine could significantly improve the health of patients who suffer from SA infections.

项目摘要：金黄色葡萄球菌(SA)，包括耐甲氧西林金黄色葡萄球菌(MRSA) 在美国，皮肤和软组织感染(SSTI)的最常见原因。SA导致复发感染，特别是在免疫功能低下的高度易感患者群体中。至到目前为止，还没有预防金黄色葡萄球菌感染的疫苗在人体试验中成功。与此同时，需要疫苗不断升级，这种病原体获得抗生素的能力也在不断提高。抵抗。我们开发了一种基于病毒样颗粒(VLP)的疫苗策略来控制SA 分泌的β-Barrel成孔毒素。在皮肤感染模型中，基于此的疫苗方法诱导抗体，防止感染发病机制，免除宿主免疫细胞和限制疾病。在这项提案中，我们的目标是评估这种疫苗策略的临床前潜力。对抗各种SAβ-Barrel致孔毒素。我们将确定疫苗的免疫原性在体内，并对金黄色葡萄球菌的定植效果。我们的结果可以为下一步的开发奠定基础预防金黄色葡萄球菌感染，限制发病机制的有效疫苗。这种疫苗可以显著改善金黄色葡萄球菌感染患者的健康状况。