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Development of a Vaccine for Staphylococcal Infections

葡萄球菌感染疫苗的开发

基本信息

批准号：
10255984
负责人：
Dominique M. Missiakas
金额：
$ 25.78万
依托单位：
IMMUNARTES LLC
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：
2021-04-16 至 2021-11-30
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/10255984
关键词：
Abscess Address Anaphylaxis Animals Antibiotic Resistance Antibiotic Therapy Antibiotics Antibodies Antibody-mediated protection B-Cell Antigen Receptor B-Lymphocytes Bacteremia Bacteria Binding Biological Biological Assay Blood Circulation Catheters Cavia Cell Degranulation Cell secretion Cells Chicago Childhood Clinical Communities Community Hospitals Cyclic GMP Detection Development Devices Disease Disease Outcome Endotoxins Escherichia coli Exhibits Fc domain Future Generations Genus staphylococcus Goals Health Histamine Release Hospitalization Hospitals Human Immune Immune Evasion Immune response Immunity Immunization Immunoblotting Immunoglobulin G Immunoglobulin Idiotypes Immunoglobulin M Immunoglobulins Immunotherapeutic agent Immunotherapy Individual Infection Lead Lesion Lung infections Mediating Membrane Proteins Molecular Mus Natural Immunity Nosocomial Infections Operative Surgical Procedures Outcome Outpatients Paste substance Patients Phase Population Prevalence Preventive Preventive vaccine Process Production Property Proteins Public Health Recurrence Research Residual state Resistance Risk Risk Factors Safety Sales Sepsis Skin Tissue Small Business Technology Transfer Research Soft Tissue Infections Staphylococcal Infections Staphylococcal Protein A Staphylococcus aureus Staphylococcus aureus infection Structure of mucous membrane of nose Superantigens Surface Surgical Wound Infection Testing Time Treatment Efficacy United States United States Food and Drug Administration Universities Vaccinated Vaccine Design Vaccines Variant Visit Work adaptive immune response cell bank clinical efficacy clinically significant commercial application cost crosslink design efficacy testing improved improved outcome mast cell methicillin resistant Staphylococcus aureus mortality mouse model neutralizing antibody novel therapeutics pathogen preclinical development preclinical efficacy preclinical safety prevent programs public health relevance receptor recurrent infection response safety study safety testing skeletal soft tissue therapeutic vaccine vaccine candidate vaccine development vaccine-induced immunity ventilator-associated pneumonia virtual

项目摘要

Project Summary / abstract: Staphylococcus aureus causes skin and soft tissue infections (SSTI) that result in 14.2 million outpatient visits per year and 850,000 hospital admissions. S. aureus infection is not associated with the development of immunity and, even with surgical and antibiotic therapy, recurrent infections occur frequently. Infections with antibiotic-resistant S. aureus strains, designated MRSA (methicillin-resistant S. aureus) are associated with poor disease outcomes and are now identified in 22% of hospital isolates. In order to address the public health crisis of MRSA, we are developing a vaccine to prevent invasive S. aureus infections. Key features of S. aureus disease are the pathogen’s resistance to opsonophagocytic killing (OPK) and the suppression of the host’s adaptive immune responses. Staphylococcal binding to immunoglobulin (Ig) is mediated by staphylococcal protein A (SpA), a surface protein that associates with the Fc-domain of IgG and the heavy chain of VH3 clan IgG and IgM. While the former activity provides protection from antibodies that induce OPK, the latter, through the crosslinking of IgM receptors, triggers proliferation and B cells and secretion of non- protective VH3 antibodies, thereby disrupting adaptive immune responses and the development of protective immunity. We have developed SpA*, a vaccine that elicits SpA-neutralizing antibodies that effectively promote OPK of the pathogen while also allowing the host to generate many different pathogen specific antibodies that together eliminate S. aureus colonization and reduce the risk of invasive disease. This phase I STTR proposal aims to establish the feasibility of generating the SpA* vaccine by establishing its preclinical safety and biological efficacy.

项目摘要/摘要：