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Infect Immun, August 1998, p. 3990-3994, Vol. 66, No. 8
0019-9567/98/$04.00+0
Copyright © 1998, American Society for Microbiology. All rights reserved.

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

J. Staczek,1 * H. E. Gilleland Jr.,1 L. B. Gilleland,1 R. N. Harty,2 A. García-Sastre,2 O. G. Engelhardt,2 and P. Palese2

Department of Microbiology and Immunology, Louisiana State University Medical Center, School of Medicine in Shreveport, Shreveport, Louisiana 71130-3932,1 and Department of Microbiology, Mount Sinai School of Medicine, New York, New York 10029-65742

Received 18 March 1998/Returned for modification 30 April 1998/Accepted 24 May 1998

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 × 103 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.

* Corresponding author. Mailing address: Department of Microbiology and Immunology, Louisiana State University Medical Center, School of Medicine in Shreveport, 1501 Kings Highway, Shreveport, LA 71130-3932. Phone: (318) 675-5757. Fax: (318) 675-5764. E-mail: Jstacz{at}lsumc.edu.

Infect Immun, August 1998, p. 3990-3994, Vol. 66, No. 8
0019-9567/98/$04.00+0
Copyright © 1998, American Society for Microbiology. All rights reserved.


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Copyright © 1998 by the American Society for Microbiology. All rights reserved.