Dr. Paul Arnaboldi Receives $500,000 NIH Grant to Support Respiratory Vaccine Development
The Funding Will Support Research to Combat Pseudomonas aeruginosa, a Prominent Cause of Fatal Healthcare-Acquired Infections
Paul Arnaboldi, Ph.D., associate professor of pathology, microbiology, and immunology, has been awarded a $523,692 grant from the National Institutes of Health (NIH) to support the development of a respiratory mucosal vaccine to combat Pseudomonas aeruginosa (PA), a prominent cause of fatal health care-acquired infections, serious burn wound infections, and chronic lung infection in cystic fibrosis patients.
“The spread of multi-antibiotic resistant PA has made infections with this opportunistic pathogen increasingly difficult to treat,” says Dr. Arnaboldi. “This vaccine would help to prevent death from infection in individuals with higher risks for PA infections, including long-term care facility residents, cystic fibrosis patients, surgical patients, those who are planned to receive immunosuppressive therapies, such as cancer or transplant patients, the elderly, and individuals at high risk for burn wounds.”
PA, which is considered a critical threat to public health by the World Health Organization and the Centers for Disease Control and Prevention, is one of the most common causes of ventilator-associated pneumonia, and a top ten cause of surgical site infections, catheter-associated urinary tract infections, and blood infections from central lines.
“While most vaccines are given parenterally via injection, this route of administration does not provide strong protection at mucosal surfaces, the site of entry for most pathogens, including PA. Mucosal vaccination provides strong protection both systemically and at mucosal sites, such as the respiratory tract,” says Dr. Arnaboldi.
To address this, he and his research team are developing an intranasal protein subunit vaccine against PA, using the tobacco mosaic virus (TMV) as a delivery platform. TMV is a plant pathogen that does not infect animal cells and is highly immunogenic, being an optimal size and composition for recognition by the immune system. The modified version of the TMV has an extra lysine on its surface, making it possible to attach vaccine antigens directly to the virus. In early tests, which showed positive results, this modified TMV was used to deliver PcrV—a protein found at the tip of the PA type III secretion system—along with an adjuvant called curdlan, which encourages an immune response.
Dr. Arnaboldi and his fellow researchers are now working to define additional vaccine antigens to create a multi-valent vaccine that will provide broad protection against multiple strains of PA and additional pathways that can be targeted to improve vaccine efficacy.
