Enhancement of the protective efficacy of anoprFDNA vaccine againstPseudomonas aeruginosa

Abstract

The outer membrane protein F gene (oprF) of Pseudomonas aeruginosa was recently shown by us to protect mice from P. aeruginosa chronic pulmonary infection when used as a DNA vaccine administered by three biolistic (gene gun) intradermal inoculations given at 2-week intervals. In the present study, we used two different strategies to improve the protective efficacy of the DNA vaccine. In the first strategy, mice were primed with two biolistic intradermal inoculations with the oprF vaccine and then were given a final intramuscular booster immunization containing either a synthetic peptide-keyhole limpet hemocyanin (KLH) conjugate or a chimeric influenza virus. Both the synthetic peptide conjugate and the chimeric virus contained peptide 10, a previously identified immunoprotective epitope of protein F. The second strategy involved the addition of a second outer membrane protein to the vaccine. DNA encoding a fusion protein comprised of the C-terminal half of protein F fused to OprI was administered by three biolistic intradermal inoculations. Challenge with P. aeruginosa in a chronic pulmonary infection model demonstrated that boosting with the chimeric virus (but not with peptide-KLH) or adding oprI to the DNA vaccine significantly enhanced protection as compared to that afforded by the oprF vaccine given alone. Thus, both strategies appear to augment the protection afforded by an oprF-only DNA vaccine.

Understanding Pseudomonas aeruginosa–Host Interactions: The Ongoing Quest for an Efficacious Vaccine

“…DNA immunisation with OprF also showed potential, eliciting OprF-specific IgG1 opsonic antibodies that reduced bacterial burden in the lungs of a mouse model of chronic pulmonary infection [192]. Protective capacity was substantially enhanced by one of two strategies: (i) a booster immunisation using a chimeric influenza virus that contains an immunoprotective epitope of OprF, or (ii) immunisation with a DNA vaccine that contained an OprI-OprF gene-fusion construct [193,194]. Recently, Gong et al compared four DNA vaccines with oprL and oprF genes as monovalent vaccines, a fusion OprL-OprF vaccine or a divalent combination (OprL and OprF).…”

Immunization with 3-oxododecanoyl-l-homoserine lactone–protein conjugate protects mice from lethal Pseudomonas aeruginosa lung infection

“…Sawa and collaborators have reported a type III secretion apparatus, PcrV, a unique system that injects bacterial toxin into eukaryotic cells, as a new vaccine target, and immunization against PcrV ensures the survival of challenged mice and decreased lung inflammation and injury (Sawa et al, 1999). More recently, the protective efficacy of DNA vaccines against outer-membrane protein F has been reported in a mouse model of chronic lung infection due to P. aeruginosa (Price et al, 2002;Staczek et al, 2003). However, there is currently no approved vaccine against P. aeruginosa infections in the clinical setting.…”