A chimeric influenza virus expressing an epitope of outer membrane protein F of Pseudomonas aeruginosa affords protection against challenge with P. aeruginosa in a murine model of chronic pulmonary infection.
The ability of a chimeric influenza virus containing, within the antigenic B site of its hemagglutinin, an 11-amino-acid (AEGRAINRRVE) insert from the peptide 10 epitope of outer membrane (OM) protein F of Pseudomonas aeruginosa to serve as a protective vaccine against P. aeruginosa was tested by using the murine chronic pulmonary infection model. Mice immunized with the chimeric virus developed antibodies that reacted in an enzyme-linked immunosorbent assay with peptide 10, with purified protein F, and with whole cells of various immunotype strains of P. aeruginosa but failed to react with a protein F-deficient strain of P. aeruginosa. The chimeric-virus antisera reacted specifically with protein F alone when immunoblotted against proteins extracted from cell envelopes of each of the seven Fisher-Devlin immunotype strains and had significantly greater in vitro opsonic activity for P. aeruginosa than did antisera from wild-type influenza virus-immunized mice. Subsequent to intratracheal challenge with agar-encased cells of P. aeruginosa, chimeric-virus-immunized mice developed significantly fewer severe lung lesions than did control mice immunized with the wild-type influenza virus. Furthermore, the chimeric influenza virus-immunized group had a significantly smaller percentage of mice with >5 x 10(3) CFU of P. aeruginosa in their lungs upon bacterial quantitation than did the control group. These data indicate that chimeric influenza viruses expressing epitopes of OM protein F warrant continued development as vaccines to prevent pulmonary infections caused by P. aeruginosa.
Department of Microbiology and Immunology, Louisiana State University Medical Center, School of Medicine in Shreveport, Shreveport, Louisiana 71130-3932, USA. Jstacz@lsumc.edu
J
J
Staczek
H E
HE
Gilleland
L B
LB
Gilleland
R N
RN
Harty
A
A
García-Sastre
O G
OG
Engelhardt
P
P
Palese
D000907:Antibodies, Bacterial / Q000276:immunology; D000942:Antigens, Bacterial / Q000235:genetics / Q000276:immunology; D001428:Bacterial Vaccines / Q000276:immunology*; D004195:Disease Models, Animal; D018985:Epitopes, B-Lymphocyte / Q000235:genetics / Q000276:immunology*; D005822:Genetic Vectors; D006801:Humans; D009980:Influenza A virus; D008171:Lung Diseases / Q000276:immunology* / Q000517:prevention & control; D018272:Porins / Q000235:genetics / Q000276:immunology*; D011552:Pseudomonas Infections / Q000517:prevention & control*; D014614:Vaccines, Synthetic / Q000276:immunology
D000907:Antibodies, Bacterial; D000942:Antigens, Bacterial; D001428:Bacterial Vaccines; D018985:Epitopes, B-Lymphocyte; D018272:Porins; D014614:Vaccines, Synthetic