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，可引起严重感染烧伤、重伤、肺炎患者以及需要插管或手术的危重患者导管插入术。由于抗生素耐药性，清除 Pa 很困难。约有 32,600 例多重药物滥用病例耐药 (MDR) Pa 每年导致 2700 例住院患者死亡，患者护理费用达 7.57 亿美元。此外，Pa 是囊性纤维化 (CF) 患者肺部感染的主要原因，其中 >70% 人口长期被青少年殖民。军事人员受到事件的严重影响 MDR Pa 在战斗相关伤害中的应用。同样重要的是，负面影响的最大风险因素与 MDR Pa 感染相关的结果是高龄。 60岁以后明显增加 MDR Pa 感染导致的发病率和死亡率。因此，具有广泛保护性的Pa疫苗具有广阔的市场最多可接种三种疫苗，为所有人提供全面保护。数亿每年都会给予疫苗剂量，销售额接近约 5B 美元。虽然 Pa 疫苗正在开发中，没有一个获得许可。我们技术的目标是一种预防性疫苗，可以预防最初的感染 Pa 定植，无论血清型如何，以保护弱势患者，我们的目标是用于本研究的成熟成虫，在生物膜形成和宿主适应之前。当第一阶段完成后，我们将优化疫苗配方，并在小鼠和兔子模型中证明保护功效。