Properties determining the potential of naturally occurring and vaccine-induced human antibodies to protect against lethal infection of Pseudomonas aeruginosa

Abstract

In order to characterize antibodies responsible for the protection against fatal infection with Pseudomonas aeruginosa we analysed the fine specificity, avidity and protective capacities of naturally occurring anti-lipopolysaccharide (LPS) antibodies in two standard human Ig preparations and of vaccine-induced anti-LPS antibodies in a hyperimmune Ig preparation. Applying competitive binding assays, immunoblotting and an in vivo protection assay, we provide evidence that only preparations from immunized volunteers contain significant amounts of antibodies which confer detectable protection in a murine burn-wound model. Supported by the parallel analysis of monoclonal antibodies, our data suggest that protection by passive immunization with anti-LPS antibodies is mediated by antibodies specific for the LPS O-chain moiety of the corresponding virulent bacterium. Furthermore, our results indicate that protectiveness is restricted to a small population of antibodies with high affinity for particular O-chain epitopes.