Enhancement of the protective efficacy of an oprF DNA vaccine against Pseudomonas aeruginosa.
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.
Price
Brian M
BM
Department of Microbiology, The Ohio State University, 484 West 12th Ave., Columbus, OH 43210-1292, USA.
Barten Legutki
J
J
Galloway
Darrell R
DR
von Specht
Bernd Ulrich
BU
Gilleland
Linda B
LB
Gilleland
Harry E
HE
Staczek
John
J
D000818:Animals; D000907:Antibodies, Bacterial / Q000097:blood*; D001428:Bacterial Vaccines / Q000008:administration & dosage / Q000276:immunology*; D002908:Chronic Disease; D004195:Disease Models, Animal; D005260:Female; D006433:Hemocyanins / Q000235:genetics / Q000276:immunology; D006801:Humans; D007115:Immunization Schedule; D007117:Immunization, Secondary; D008171:Lung Diseases / Q000382:microbiology / Q000517:prevention & control*; D051379:Mice; D008807:Mice, Inbred BALB C; D009895:Opsonin Proteins / Q000378:metabolism; D009975:Orthomyxoviridae / Q000235:genetics / Q000276:immunology / Q000378:metabolism; D010455:Peptides / Q000138:chemical synthesis / Q000235:genetics / Q000276:immunology; D018272:Porins / Q000737:chemistry / Q000235:genetics / Q000276:immunology* / Q000378:metabolism; D011552:Pseudomonas Infections / Q000382:microbiology / Q000517:prevention & control; D011550:Pseudomonas aeruginosa / Q000235:genetics / Q000276:immunology*; D011993:Recombinant Fusion Proteins / Q000276:immunology; D019444:Vaccines, DNA / Q000008:administration & dosage / Q000276:immunology*
D000907:Antibodies, Bacterial; D001428:Bacterial Vaccines; D009895:Opsonin Proteins; D010455:Peptides; D018272:Porins; D011993:Recombinant Fusion Proteins; D019444:Vaccines, DNA; D006433:Hemocyanins; C032808:keyhole-limpet hemocyanin