BOSTON, MA—Researchers at Brigham and Women's Hospital (BWH) have discovered a new vaccine candidate for the bacterium Pseudomonas aeruginosa taking advantage of a new mechanism of immunity.
The study was published online in the American Journal of Respiratory and Critical Care Medicine on June 21, 2012.
Pseudomonas aeruginosa is a leading cause of hospital-acquired infections, particularly in patients on respirators, where it can cause so-called ventilator-associated pneumonia, which carries a very high mortality rate. Pseudomonas also causes lung infections in people with cystic fibrosis, a genetic disorder that renders the lungs susceptible to bacterial infection.
Despite more than 40 years of vaccine research and development, there is no clinically available vaccine for this bacterium. Most prior vaccine efforts have focused on generating antibodies to Pseudomonas toxins or surface molecules, especially the sugar coating on the bug called the lipopolysaccharide O antigen. These approaches have not yielded a licensed vaccine for humans.
Gregory Priebe, MD, BWH Division of Infectious Diseases, Department of Medicine, and Boston Children's Hospital Division of Critical Care Medicine, Department of Anesthesiology, Perioperative and Pain Medicine, along with researchers from Harvard Medical School, constructed a vaccine based on a new mechanism of immunity to Pseudomonas mediated by T helper 17 (Th17) cells. Th17 cells are a recently described type of helper T cells that secrete the cytokine IL-17 and enhance antibacterial mucosal defenses.
In the current studies, the investigators designed a screen for Th17-stimulating protein antigens expressed by a molecular library of DNA encoding Pseudomonas proteins. The screen discovered that the Pseudomonas protein PopB is a very effective stimulator of Th17 immunity, and immunization with purified PopB protected mice from lethal pneumonia in an antibody-independent fashion.
The researchers are currently taking their work a step further by constructing conjugate vaccines using PopB as a protein carrier with the hopes of improving the effectiveness of the vaccine. They hope that the PopB-based vaccine might one day be used to prevent Pseudomonas infections in hospitalized patients and in people with cystic fibrosis.
This research was supported by grants from the National Institutes of Health (HL092515).
Brigham and Women's Hospital (BWH) is a 793-bed nonprofit teaching affiliate of Harvard Medical School and a founding member of Partners HealthCare. BWH has more than 3.5 million annual patient visits, is the largest birthing center in New England and employs nearly 15,000 people. The Brigham's medical preeminence dates back to 1832, and today that rich history in clinical care is coupled with its national leadership in patient care, quality improvement and patient safety initiatives, and its dedication to research, innovation, community engagement and educating and training the next generation of health care professionals. Through investigation and discovery conducted at its Biomedical Research Institute (BRI), BWH is an international leader in basic, clinical and translational research on human diseases, involving nearly 1,000 physician-investigators and renowned biomedical scientists and faculty supported by nearly $625 million in funding. BWH continually pushes the boundaries of medicine, including building on its legacy in organ transplantation by performing the first face transplants in the U.S. in 2011. BWH is also home to major landmark epidemiologic population studies, including the Nurses' and Physicians' Health Studies, OurGenes and the Women's Health Initiative. For more information and resources, please visit BWH's online newsroom.
Journal
American Journal of Respiratory and Critical Care Medicine