Vaccines for Pseudomonas aeruginosa
Abstract
War trauma-associated wound infections and hospital-acquired infections due to the bacterium Pseudomonas aeruginosa are a significant threat to the health of military personnel. The high and increasing antibiotic resistance of this bacterium, coupled with the failure of prior vaccine development efforts and the lack of new antibiotics in the pharmaceutical industry’s pipeline, all call for new approaches to vaccine design. This FY18 PRMRP Investigator-Initiated Research Award proposes to formulate new vaccines for Pseudomonas by combining bacterial proteins and sugars that stimulate multiple different types of immunity to work together to give the best protection from infection. One of the proteins induces a recently discovered mechanism of immunity made up of Th17 cells, which are helper T cells that secrete a cytokine called IL-17. IL-17 helps kill the bacteria by quickly bringing in other immune cells called phagocytes to the site of infection. Since IL-17 works by an indirect mechanism of protection, the bacteria are unlikely to become resistant to these Th17-based vaccines, and the vaccines might even protect against mixed infections of Pseudomonas with other bacteria, including common pathogens found in these settings that can also be controlled by Th17 responses such as Staphylococcus aureus. Compared to antibody-based therapies or prevention measures, the active vaccines developed in this project should be more effective since active vaccines can stimulate T cell immunity, are less likely to be evaded by bacterial mutations, and are logistically easier to administer. The FY18 PRMRP Topic Area covered in this project is Vaccine Development for Infectious Disease. In the short term, these studies will yield a lead candidate vaccine that will be positioned for preclinical development by the end of the funding period, with human studies following soon afterwards. We have already shown that human immune cells in the blood can recognize the Pseudomonas protein contained in our vaccine. A major objective of the project is to find vaccine formulations and adjuvants that have maximal Th17 responses with minimal side effects and that also achieve broad protection from multiple types of Pseudomonas infections in mice. We will also test the duration of immunity in mice. In the long term, this project will benefit military personnel by preventing Pseudomonas infections in those who are afflicted by combat-related burns or wounds or who require hospitalization. This will not only save lives and limbs but will also decrease healthcare costs by lowering infection-associated hospital length of stay.
Document Details
- Document Type
- DoD Grant Award
- Publication Date
- Nov 19, 2019
- Source ID
- W81XWH1910208
Entities
People
- Gregory Priebe
Organizations
- Boston Children's Hospital
- United States Army