ADJUVANTICITY OF ISCOMS INCORPORATING A T-CELL-REACTIVE LIPOPROTEIN OF THE FACULTATIVE INTRACELLULAR PATHOGEN FRANCISELLA-TULARENSIS

Immunostimulating complexes (ISCOMs) are known to be highly effective adjuvants for envelope antigens of viral agents, but have not been eva luated for use with antigens of intracellular bacteria. Balb/c mice we re subcutaneously immunized with ISCOMs into which the T cell-reactive membrane protein TUL4 of Francisella tularensis had been incorporated . Spleen cells from the immunized mice responded in vitro to TUL4 and to heat-killed F. tularensis live vaccine strain (LVS) with proliferat ion and production of gamma-interferon, whereas spleen cells from cont rol mice immunized with TUL4 only did not respond to the antigens. Whe n mice immunized with TUL4 ISCOMs, were challenged with F. tularensis LVS, bacterial counts in spleen and liver were lower than in non-immun ized mice. Again, TUL4 had no effect when used without ISCOMs. When pr oteins of a total membrane preparation of F. tularensis LVS were incor porated in ISCOMs and used for immunization, a decrease in bacterial c ounts was obtained which was similar in magnitude to that of TUL4 ISCO Ms. Generally, the adjuvant effects demonstrated did not compare with the excellent protective effect of live tularaemia vaccine, Nonetheles s, ISCOMs provide a means whereby protective antigens of F. tularensis can be tested.