Splenocytes from mice primed with influenza virus envelope proteins incorporated in iscoms, as micelles or as infectious virus, were restimulated in vitro with the same antigen. Interleukin-2 (IL-2) and interferon-gamma (IFN-gamma) were assayed in the supernatants of such cultures. Influenza virus iscoms induced IL-2 and IFN-gamma responses in restimulation experiments that were antigen specific and significantly higher than those induced by micelles or infectious virus. Serum samples collected at the end of the experiments were analysed for the antibody response and profile. The antibody titres induced by iscoms were of a similar order of magnitude as those induced by infectious virus, and were about 18 times higher than the titres induced by micelles. In mice immunized with iscoms or infectious virus the most abundant antibodies were of the IgG1 and IgG2a isotype, and the IgE response was low. We conclude that immunization with iscoms stimulates the Th1-like subtype of murine T lymphocytes.

SUMMARYAn experimental influenza virus {A/PR/8/34{HINI)) vaccine was icstcd and evaluated in mice. The mice were inoculated once or twice intranasally or Bubcutancously with I or lO/igofiscoms prior to ehallenge with high doses oflive virus. It was demonstrated that two intranasal administrations were as efficient as two s.e. administrations, both routes inducing high levels of aniibody and protection against challenge infection. With a one-dose regimen, the s.e. route induced a somewhat higher antibody response than ihe inlranasal route; this might be explained by technical difficulties connected with an inlranasal administration.

SUMMARYThe kinetics ofthe expression of membrane-associated IL-1 (mIL-1) and soluble IL-1 (sIL-1) was studied in in vitro stimulated spleen cells from non-primed mice or from mice primed with influenza virus antigens incorporated in the immuno-stimulating complexes (iscoms) or as micelles. Matrix, which is the carrier structure for the antigens in the iscom, was used as a non-antigen stimulus. The IL-1 produced was assayed in an I L-l-dependent cell line and the specificity was demonstrated in a blocking experiment with antiserum to IL-la. Soluble IL-la was also quantified in ELISA. Iscoms and matrix induced production of mIL-1 and sIL-l in cultures from non-treated mice as well as from mice primed 4 days before with iscoms or micelles. Micelles were a less strong stimulus and did not induce production of sIL-1. Micelles induced production of mIL-1 in cultures from non-primed mice or from mice which were recently immunized with micelles. No mIL-l expression was induced by micelles if the spleen cells originated from mice immunized shortly before with iscoms. Depletion experiments demonstrated that sIL-1 was produced by adherent cells upon stimulation with iscoms or matrix. However, factor(s) from the non-adherent cells seem to be necessary for optimal secretion ofslL-1.