Pseudomonas aeruginosa (Pa) is a deadly bacteria that is strongly associated with wound infections, particularly in the setting of immunocompromised hosts such as diabetics and hospitalized patients. Due to worsening antibiotic resistance, it has become increasingly difficult to treat Pa infections. I recently described a novel vaccine that may protect against Pa infections. The antigenic target of this vaccine is a bacteriophage ? a virus that is produced by Pa. Unlike lytic phages that lyse their bacterial hosts and can be used in phage therapy, Pf phage is a temperate phage that contributes to Pa fitness and virulence. In particular, Pf phage act as structural elements that promote the formation of biofilms and promote the establishment of Pa infections. Building on this insight, we showed that vaccinating mice with a peptide sequence from the major coat protein (CoaB) of Pf phage as well as passive immunization with anti-Pf phage monoclonal antibodies prevents Pa wound infections. However, much work remains before this vaccine can be used to prevent Pa wound infections in humans. My hypothesis is that humoral immunity against Pf promotes phagocytosis of Pa and is protective against Pa wound infections in humans.
In Aim 1, I will use a mouse Pa wound infection model to evaluate the effect of anti-Pf antibodies on phagocytosis, opsonization, and clearance of Pa.
In Aim 2, I will determine the effectiveness of anti-Pf antibodies against multiple clinical strains of Pa.
In Aim 3, I will examine the presence of anti-Pf phage antibodies in human patients with Pa wound infections. I am currently a fellow in Dr. Paul Bollyky?s laboratory in the Division of Infectious Diseases at Stanford University. Stanford University offers an exceptional scientific environment where I have all the resources that will be essential to the success of this project. My long-term goal is to become an independent physician-scientist with a research focus on development of vaccines and immune therapeutics to target resistant microorganisms. To achieve this goal, I have developed a customized career development plan that incorporates both formal and informal training. This training plan draws upon my existing expertise in immunology, and will enhance my expertise in vaccine immunology, bacteriophage microbiology, and epidemiology. The planned didactics and technical training included here will provide the foundation necessary to become a successful independent researcher.
We recently reported that immunization against Pf bacteriophage (Pf), a virus produced by Pseudomonas aeruginosa (Pa), can protect against Pa wound infections. In my K08 project I will evaluate this vaccine in wound infection models and determine the role that antibodies against Pf play in the clearance and prevention of Pa wound infections. These studies will lay the preclinical groundwork for development of the first vaccine targeting a bacteriophage and launch my career in vaccine immunology.
