Induction of Opsonic Antibodies to Pseudomonas aeruginosa Mucoid Exopolysaccharide by an Anti-idiotypic Monoclonal Antibody

Abstract

Mucoid strains of Pseudomonas aeruginosa are the major pulmonary pathogens for cystic fibrosis patients. Opsonizing antibodies to the mucoid exopolysaccharide (MEP) antigen may protect animals and some cystic fibrosis patients from infection. However, MEP does not readily elicit opsonic antibodies either during chronic infection or after vaccination. To evaluate alternative means to induce opsonic antibodies, a murine monoclonal anti-idiotypic antibody directed to an opsonic monoclonal antibody specific to MEP was produced. The anti-idiotypic antibody bound to F(ab')² fragments of the opsonic antibody, blocked binding to MEP, bound to crossreactive idiotopes on human opsonic antibodies to MEP, and elicited MEP-specific antibodies in syngeneic and allogeneic mice. These anti-idiotype-induced, MEP-specific antibodies fixed complement to mucoid P. aeruginosa cells and opsonized them for phagocytic killing by human leukocytes. These studies demonstrate the potential utility of anti-idiotypic monoclonal antibody for generating protective immunity against bacterial polysaccharides.