Characterizing Monoclonal Antibodies as a Novel Therapeutic for Pseudomonas aeruginosa Infections.

Aaron C. Malkowski*, Alexander M. Horspool, Emel Sen-Kilic, Scott L. Breslow and Mariette Barbier, West Virginia University Vaccine Development Center, West Virginia University, Morgantown, WV 26506

Field (Broad Category): Medical Sciences (Oral-Science & Technology) 

Student’s Major: Immunology and Medical Microbiology 

Pseudomonas aeruginosa is a Gram-negative rod-shaped bacterium, and a causative agent in urinary tract, ear, and skin infections, as well as acute and chronic lung infections. As an antimicrobial-resistant pathogen with no approved vaccines or immunotherapies, alternative therapeutics are urgently needed. Recently we have shown that an acellular vaccine, targeting the iron-acquisition protein FpvA, protects against Pseudomonas aeruginosa infection. The vaccine induces antibody production against the bacterium which we can purify to generate specific immunotherapies against P. aeruginosa. Monoclonal antibodies (mAbs) could prove useful as a treatment for P. aeruginosa infections and an alternative to antibiotics. We hope to produce our own mAb therapy to P. aeruginosa using antibodies generated in response to our FpvA vaccine. After immunizing mice with the acellular FpvA vaccine, we isolated antibody-producing splenocytes and created using cell-to-cell fusion stable, mAb-producing colonies of cells called hybridomas. Several mAb candidates have been identified, which we have begun to characterize as novel treatments to P. aeruginosa infections. We performed in vitro functional assays to characterize these antibodies. Assays performed measured characteristics of the mAbs, such as binding to FpvA or P. aeruginosa and determining their function in vitro. Our results from these assays provide the basis for testing antibodies in vivo, and for other critical pre-clinical studies. 

Funding: Cystic Fibrosis Foundation; WVU MICB Department; WVU Vaccine Development Center 

Program/mechanism supporting research/creative efforts: An External Internship or Other Type of Program