Liposome encapsulation of a soluble recombinant fragment of the respiratory syncytial virus (RSV) G protein enhances immune protection and reduces lung eosinophilia associated with virus challenge

Respiratory syncytial virus (RSV) is a leading cause of bronchiolitis and p neumonia in young children and infants. Previous animal studies have shown that immunizing intramuscularly or intraperitoneally with the RSV G protein has elicited protective as well as harmful immune responses upon RSV chall enge. In an RSV immunization strategy designed to target the respiratory tr act directly (the site of RSV replication), we immunized BALB/c mice intran asally with a liposome-encapsulated, prokaryotically expressed thioredoxin fusion protein consisting of amino acids 128-229 of the RSV G protein (Trx- G(128-229)) Upon intranasal challenge with RSV, a 100 to 500-fold reduction in lung RSV replication was observed in mice immunized with liposome-encap sulated Trx-G(128-229) compared to a sham-immunized control group. Analysis of bronchoalveolar lavage fluids revealed an influx of eosinophils (18% of total cells) in mice immunized with Trx-G(128-229) alone. Such eosinophili c infiltration was diminished (to 4.5% of total cells), however, in mice im munized with liposome-encapsulated Trx-G(128-229). Histological analysis of lung tissue revealed an accumulation of cells around the bronchioles and v essels in mice immunized with Trx-G(128-229) alone followed by RSV challeng e which was not increased further in mice immunized with liposome-encapsula ted Trx-G(128-229) These results show that intranasal immunization of BALB/ c mice with Trx-G(128-229), when encapsulated in liposomes, can reduce the level of RSV replication in the lung as well as specifically reduce the deg ree of eosinophilic infiltration compared to mice immunized with Trx-G(128- 229) alone. This demonstrates the potential of liposomes and particular rec ombinant fragments of the RSV G protein as an effective combination in RSV vaccine studies. (C) 2000 Elsevier Science Ltd. All rights reserved.