RECOMBINANT VACCINIA VIRUS COEXPRESSING THE F-PROTEIN OF RESPIRATORY SYNCYTIAL VIRUS (RSV) AND INTERLEUKIN-4 (IL-4) DOES NOT INHIBIT THE DEVELOPMENT OF RSV-SPECIFIC MEMORY CYTOTOXIC T-LYMPHOCYTES, WHEREAS PRIMING IS DIMINISHED IN THE PRESENCE OF HIGH-LEVELS OF IL-2 OR GAMMA-INTERFERON

In order to investigate if immune responses to the fusion (F) protein of respiratory syncytial virus (RSV) could be influenced by cytokines, recombinant vaccinia viruses (rVV) carrying both the F gene of RSV an d the gene for murine interleukin-2 (IL-2), IL-4, or gamma interferon (IFN-gamma) were constructed. In vitro characterization of rVV reveale d that insertion of the cytokine gene into the VP37 locus of the vacci nia virus genome resulted in 100- to 1,000-fold higher expression than insertion of the same gene into the thymidine kinase (TK) locus, In c omparison, only a two- to fivefold difference in the level of expressi on of the F protein was observed when the gene was inserted into eithe r of these two loci. Mice vaccinated with rVV expressing the F protein and high levels of IL-2 or IFN-gamma cleared rVV more rapidly than mi ce inoculated with a control rVV and developed only low levels of RSV- specific serum antibody. In addition, these recombinants were much les s effective at priming RSV-specific memory cytotoxic T lymphocytes (CT L) and IFN-gamma production by spleen cells than rVV expressing the F protein alone. In contrast, mice vaccinated with rVV expressing high l evels of IL-4 showed signs of delayed rVV clearance. RSV-specific seru m antibody responses were biased in favor of immunoglobulin G1 (IgG1) in these mice, as there was a significant reduction in IgG2a antibody responses compared with serum antibody responses in mice vaccinated wi th rVV expressing the F protein alone. However, vaccination with rVV e xpressing the F protein together with high levels of IL-4 did not alte r the development of RSV-specific memory CTL or IFN-gamma production b y RSV-restimulated splenocytes.