A CHIMERIC INFLUENZA-VIRUS EXPRESSING AN EPITOPE OF OUTER-MEMBRANE PROTEIN-F OF PSEUDOMONAS-AERUGINOSA AFFORDS PROTECTION AGAINST CHALLENGEWITH PSEUDOMONAS-AERUGINOSA IN A MURINE MODEL OF CHRONIC PULMONARY INFECTION

The ability of a chimeric influenza virus containing, within the antig enic B site of its hemagglutinin, an Il-amino-acid (AEGRAINRRVE) inser t from the peptide 10 epitope of outer membrane (OM) protein F of Pseu domonas aeruginosa to serve as a protective vaccine against P. aerugin osa was tested by using the murine chronic pulmonary infection model. Mice immunized with the chimeric virus developed antibodies that react ed in an enzyme-linked immunosorbent assay with peptide 10, with purif ied 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 p rotein F alone when immunoblotted against proteins extracted from cell envelopes of each of the seven Fisher-Devlin immunotype strains and h ad significantly greater in vitro opsonic activity for P. aeruginosa t han did antisera from wild-type influenza virus-immunized mice. Subseq uent to intratracheal challenge with agar-encased cells of P. aerugino sa, chimeric-virus-immunized mice developed significantly fewer severe lung lesions than did control mice immunized with the wild-type influ enza 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 exp ressing epitopes of OM protein F warrant continued development as vacc ines to prevent pulmonary infections caused by P. aeruginosa.