Impact of molecular biology on Pseudomonas aeruginosa immunization

Abstract

Persisting high mortalities from Pseudomonas aeruginosa infection have led to new strategies for treatment. In vitro and animal studies indicate that antibodies against P. aeruginosa antigens increase host defense against this infectious agent. The most effective immunogen is lipopolysaccharide (LPS) antigen; however, LPS vaccines are poorly tolerated. Furthermore, the LPS molecule does not lend itself well to production by genetic engineering. Pseudomonas aeruginosa protein antigens which might be amenable to recombinant DNA production are outer membrane proteins and exotoxin A, modified to decrease toxicity but maintain immunogenicity. Another strategy for immunization with anti-LPS P. aeruginosa antibodies is passive administration of either hyperimmune immunoglobulins (polyclonal) or monoclonal antibodies. Passive immunization offers the dual advantage of rapid protection or treatment and is well tolerated. Several monoclonal antibodies against LPS P. aeruginosa antigens have been described, including both murine and human types. Studies in animal models of infection indicate that P. aeruginosa monoclonal antibodies do protect, thus, the most feasible application of molecular biology to the problem of P. aeruginosa infection appears to be production of immunotype-specific monoclonal antibodies for immune therapy.