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.
Staczek
J
J
Department of Microbiology and Immunology, Louisiana State University Medical Center, School of Medicine in Shreveport, Shreveport, Louisiana 71130-3932, USA. Jstacz@lsumc.edu
Gilleland
H E
HE
Gilleland
L B
LB
Harty
R N
RN
García-Sastre
A
A
Engelhardt
O G
OG
Palese
P
P
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