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.
Public Health Relevance Statement: NARRATIVE Pseudomonas aeruginosa (Pa) cause severe infections in patients with burns, severe wounds, pneumonia, or undergoing nosocomial procedures. Additionally, Pa is also the major cause of pulmonary infections in cystic fibrosis patients with over 70% of them being colonized by adulthood. Preventing Pa infections, regardless of initial injury, has become more difficult with growing antibiotic resistance. This project will develop a vaccine to prevent Pa infections in target populations, especially for those of us that are aging.
Project Terms: Adult; 21+ years old; Adult Human; adulthood; Age; ages; Elderly; advanced age; elders; geriatric; late life; later life; older adult; older person; senior citizen; Aging; Antigens; immunogen; Ursidae Family; Bears; Ursidae; bear; Biochemistry; Biological Chemistry; Burn injury; Burns; burned; Catheterization; Cathetergram; Cell membrane; Cytoplasmic Membrane; Plasma Membrane; plasmalemma; Cells; Cell Body; Critical Illness; Critically Ill; Cessation of life; Death; Dendritic Cells; Veiled Cells; Emulsions; Patient Care; Patient Care Delivery; Goals; Human; Modern Man; Infection; Intubation; Lipid A; Lung; Lung Respiratory System; pulmonary; lymph nodes; Lymph Node Reticuloendothelial System; Lymph node proper; Lymphatic nodes; lymph gland; lymphnodes; Military Personnel; Armed Forces Personnel; Military; military population; Mission; Morbidity - disease rate; Morbidity; mortality; Mus; Mice; Mice Mammals; Murine; Needles; Nasal; Nasal Passages Nose; Respiratory System, Nose, Nasal Passages; Nose; Oils; Patients; Pneumonia; Proteins; P aeruginosa; P. aeruginosa; Pseudomonas pyocyanea; Pseudomonas aeruginosa; Public Health; Domestic Rabbit; Rabbits; Rabbits Mammals; Oryctolagus cuniculus; Risk Factors; Sales; Serotyping; Cell Communication and Signaling; Cell Signaling; Intracellular Communication and Signaling; Signal Transduction Systems; Signaling; biological signal transduction; Signal Transduction; Target Populations; Technology; Toxin; Vaccination; Vaccines; Water; Hydrogen Oxide; Work; Microbial Biofilms; biofilm; Antibiotic Resistance; Resistance to antibiotics; Resistant to antibiotics; antibiotic drug resistance; antibiotic resistant; Injury; injuries; improved; Procedures; Acute; Chronic; Clinical; Phase; Populations at Risk; Agonist; Germinal Center; Structure of germinal center of lymph node; treatment vaccines; vaccine for the treatment; vaccine for treatment; therapeutic vaccine; CTLA-8; CTLA8; Cytotoxic T-Lymphocyte-Associated Antigen 8; Cytotoxic T-Lymphocyte-Associated Serine Esterase 8; IL-17; IL-17A; IL17 Protein; IL17A; Interleukin 17 (Cytotoxic T-Lymphocyte-Associated Serine Esterase 8); Interleukin 17 Precursor; Interleukin-17; ETEC; enterotoxigenic E coli; enterotoxigenic E. coli; enterotoxigenic E.coli; enterotoxigenic Escherichia coli; develop a vaccine; develop vaccines; development of a vaccine; vaccine development; Animal Models and Related Studies; model of animal; model organism; Animal Model; Toxicities; Toxic effect; novel; Pathogenesis; Modeling; response; preventing; prevent; Diameter; Caliber; Homolog of Drosophila TOLL; TLR4; Toll Homologue; toll-like receptor 4; TLR4 gene; Dose; Small Business Innovation Research Grant; SBIR; Small Business Innovation Research; Type III Secretion System Pathway; T3SS; Type III Secretion System; type 3 secretion system; Vaccinated; Virulent; Teenagers; Teen; teen years; teenage; Adjuvant; Development; developmental; vaccinology; Outcome; wound; tissue wound; wounding; wounds; cystic fibrosis patients; CF patients; individuals with CF; individuals with cystic fibrosis; patients with CF; patients with cystic fibrosis; Population; human disease; mouse model; murine model; protective efficacy; multidrug-resistant Pseudomonas aeruginosa; MDR P aeruginosa; MDR P. aeruginosa; MDR Pseudomonas aeruginosa; multi-drug resistant P. aeruginosa; multi-drug resistant Pseudomonas aeruginosa; multidrug resistant P. aeruginosa; multidrug-resistant P. aeruginosa; Formulation; Pseudomonas aeruginosa pneumonia; P aeruginosa associated pneumonia; P aeruginosa caused pneumonia; P aeruginosa induced pneumonia; P aeruginosa pneumonia; P aeruginosa-associated pneumonia; P aeruginosa-caused pneumonia; P aeruginosa-induced pneumonia; P. aeruginosa associated pneumonia; P. aeruginosa caused pneumonia; P. aeruginosa induced pneumonia; P. aeruginosa pneumonia; P. aeruginosa-associated pneumonia; P. aeruginosa-caused pneumonia; P. aeruginosa-induced pneumonia; Pseudomonas aeruginosa associated pneumonia; Pseudomonas aeruginosa caused pneumonia; Pseudomonas aeruginosa induced pneumonia; Primary Infection; Preventive vaccine; Preventative vaccine; Prophylactic vaccine; care costs; Lung infections; pulmonary infections; pneumonia model; pneumonia models; Pseudomonas aeruginosa infection; P. aeruginosa infection; infected with P. aeruginosa; infected with Pseudomonas aeruginosa; human pathogen; combat injury; combat related injury; vaccine formulation
