Passive anti-PcrV treatment protects burned mice against Pseudomonas aeruginosa challenge.

The type III secretion system consists of secreted exoproducts and structural components, such as PcrV, and this system plays an important role in the virulence of Pseudomonas aeruginosa in burned hosts. The purpose of this study was to determine if passive anti-PcrV treatment would protect burned mice from fatal P. aeruginosa challenge, and to determine the type III exoproduct phenotype of the P. aeruginosa used as challenge strains. Antiserum was raised in rabbits. Mice were given a third degree burn, challenged with a lethal dose of P. aeruginosa, and treated with either anti-PcrV or control immunoglobulin intraperitoneally. Protection against three different pseudomonads was tested. Genotyping by PCR and phenotyping by immunoblots showed the P. aeruginosa strains to all be of the invasive type III phenotype: ExoS+ and/or ExoT+, ExoU-, ExoY+. Against all strains, the anti-PcrV treatment yielded significantly better survival (p<0.05) than the control immunoglobulin treatment. Duration of significant protection was improved by giving a second injection of PcrV antisera at 24h postburn. Hence, passive anti-PcrV immunization could protect burned mice against fatal challenge with P. aeruginosa of an invasive type III phenotype. This immunotherapy might be explored further as possible treatment for highly antibiotic resistant P. aeruginosa infections in burned hosts.

Differential effects of two different routes of immunization on protection against gram-negative sepsis by a detoxified Escherichia coli J5 lipopolysaccharide group B meningococcal outer membrane protein complex vaccine in a burned mouse model.

Gram-negative sepsis causes morbidity and mortality in burned patients. To determine whether immunization with core endotoxin (lipopolysaccharide) via one of two routes could protect burned mice from septic death, mice were immunized either three times subcutaneously (SC) or one time intramuscularly (IM) then two times intraperitoneally (IP) with a core-lipopolysaccharide vaccine. Control mice were immunized with either saline or an irrelevant antigen. Postimmunization, mice were immunocompromised with a 15% TBSA flame burn and challenged subeschar with Klebsiella pneumoniae or Escherichia coli. Vaccine immunization improved the survival of both E. coli- and K. pneumoniae-challenged mice when given SC but not when given IM, IP. Postimmunization, total immunoglobulin titers were elevated over preimmune titers, but titers in IM, IP-immunized mice were higher than those in SC-immunized mice. Both isotyping and flow cytometry studies indicated that sera from mice immunized via IM, IP opsonized better than sera from mice immunized via SC. Hence, this vaccine provided route-specific protection of burned mice against gram-negative sepsis; its mechanism of action was not solely dependent upon increased immunoglobulin titers or phagocytosis.