Purified lipopolysaccharide from Francisella tularensis live vaccine strain (LVS) induces protective immunity against LVS infection that requires B cells and gamma interferon

Previous results have demonstrated that nonspecific protective immunity aga inst lethal Francisella tularensis live vaccine strain (LVS) or Listeria mo nocytogenes infection can be stimulated either by sublethal infection dth b acteria or by treatment with bacterial DNA given 3 days before lethal chall enge. Here we characterize the ability of purified lipopolysaccharide (LPS) from F. tularensis LVS to stimulate similar early protective immunity. Tre atment of mice with surprisingly small amounts of LVS LPS resulted in very strong and long-lived protection against lethal LVS challenge within 2 to 3 days. Despite this strong protective response, LPS purified from F. tulare nsis LVS did not activate murine B cells for proliferation or polyclonal im munoglobulin secretion, nor did it activate marine splenocytes for secretio n of interleukin-4 (IL-4), IL-6, IL-12, or gamma interferon (IFN-gamma). Im munization of mice with purified LVS LPS induced a weak specific anti-LPS i mmunoglobulin M (IgM) response and very little IgG; however, infection of m ice with LVS bacteria resulted in vigorous IgM and IgG, particularly IgG2a, anti-LPS antibody responses. Studies using various immunodeficient mouse s trains, including LPS-hyporesponsive C3H/HeJ mice, mu MT- (B-cell-deficient ) knockout mice, and IFN-gamma-deficient mice, demonstrated that the mechan ism of protection does not involve recognition through the Lps(n) gene prod uct; nonetheless, protection was dependent on B cells as well as IFN-gamma.