Formulation of a prophylactic vaccine against Pseudomonas aeruginosa

铜绿假单胞菌预防性疫苗的配制

基本信息

批准号：
10481409
负责人：
Aaron C Nagel
金额：
$ 30万
依托单位：
HAFION, LLC
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：
2022-03-16 至 2024-02-29
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/10481409
关键词：
Acute Adjuvant Adult Age Aging Agonist Animal Model Antibiotic Resistance Antigens Biochemistry Burn injury Caliber Catheterization Cell membrane Cells Cessation of life Chronic Clinical Critical Illness Dendritic Cells Development Dose Elderly Emulsions Formulation Goals Human Infection Injury Interleukin-17 Intubation Lipid A Lung Lung infections Microbial Biofilms Military Personnel Mission Modeling Morbidity - disease rate Mus Needles Nose Oils Oryctolagus cuniculus Outcome Pathogenesis Patient Care Patients Phase Pneumonia Population Populations at Risk Preventive vaccine Primary Infection Procedures Proteins Pseudomonas aeruginosa Pseudomonas aeruginosa infection Pseudomonas aeruginosa pneumonia Public Health Risk Factors Sales Serotyping Signal Transduction Small Business Innovation Research Grant Structure of germinal center of lymph node TLR4 gene Target Populations Technology Teenagers Toxic effect Toxin Type III Secretion System Pathway Ursidae Family Vaccinated Vaccination Vaccines Virulent Water Work care costs combat injury cystic fibrosis patients enterotoxigenic Escherichia coli human disease human pathogen improved lymph nodes mortality mouse model multidrug-resistant Pseudomonas aeruginosa novel pneumonia model prevent protective efficacy response therapeutic vaccine vaccine development vaccine formulation vaccinology wound

项目摘要

SUMMARY Pseudomonas aeruginosa (Pa) is an important opportunistic human pathogen that causes severe infections in patients with burns, severe wounds, pneumonia, and critically ill patients who require intubation or catheterization. Clearing Pa is difficult due to antibiotic resistance. There are ~32,600 cases of multi-drug resistant (MDR) Pa in hospitalized patients annually with 2700 deaths and $757 million in patient care costs. Additionally, Pa is the major cause of pulmonary infections in cystic fibrosis (CF) patients with >70% of this population being chronically colonized by their teens. Military personnel are gravely impacted by the occurrence of MDR Pa in combat-related injuries. Equally important is the fact that the biggest risk factor for negative outcomes associated with infection by MDR Pa is advanced age. After age 60, there is a significant increase in morbidity and mortality resulting from MDR Pa infection. Thus, a broadly protective Pa vaccine has large market potential with up to three vaccinations providing complete protection to all humans. Hundreds of millions of vaccine doses would be given annually, approaching ~$5B in sales. While there are Pa vaccines in development, none have been licensed. The goal of our technology is a prophylactic vaccine that prevents initial colonization by Pa, regardless of serotype, to protect vulnerable patients, which we are targeting as mature adults for this study, prior to biofilm formation and host adaptation. When Phase I is completed, we will have optimized the vaccine formulation and demonstrated protective efficacy in mice and rabbit models.

概括铜绿假单胞菌（PA）是一种重要的机会性人类病原体，会引起严重的感染在烧伤的患者中，严重伤口，肺炎和需要插管或导管插入。由于抗生素耐药性，很难清除PA。有〜32,600例多药每年有2700例死亡和7.57亿美元的患者患者的抗药性（MDR）PA。此外，PA是囊性纤维化（CF）患者肺部感染的主要原因，其中> 70％人口长期被十几岁的人殖民。军事人员受到严重影响与战斗有关的伤害中的MDR PA。同样重要的是，负面的最大风险因素与MDR PA感染相关的结果是高龄。 60岁以后，大幅增加 MDR PA感染引起的发病率和死亡率。因此，广泛的保护性PA疫苗具有大型市场最多三种疫苗的潜力为所有人类提供了完整的保护。数亿疫苗剂量每年将接近约5B美元的销售额。尽管有开发PA疫苗，但没有人获得许可。我们技术的目的是一种预防性疫苗，可防止最初 PA由PA殖民（无论血清型如何在生物膜形成和宿主适应之前，这项研究成熟的成年人。一阶段完成后，我们将优化疫苗配方，并在小鼠和兔模型中表现出保护作用。