Antibody-mediated protection against lethal respiratory tularemia (47.5)

Abstract

Abstract It has been previously shown that B cells are necessary and LPS-specific antibodies are sufficient for vaccine-induced immunity to Francisella tularensis, suggesting that antibodies play a major role in protection against tularemia. However, due to the intracellular nature of the bacterium, it is widely believed that T cells, but not antibodies, are critical for protection. We assessed the relative contribution of serum antibodies in protection against respiratory tularemia by investigating the ability of serum antibodies to clear bacteria from the lungs of intranasally infected mice and prevent systemic infection. Passive administration of immune serum collected from immunized mice was found to confer protection to naïve mice against lethal F. tularensis (LVS) challenge. Adoptively transferred antibodies rapidly cleared bacteria from the lungs and prevented spread of bacteria to liver and spleen. This protection was dependent on FcγRs and phagocytes such as macrophages and neutrophils, but not complement. Interestingly, phagocytosis and killing of opsonized bacteria was dependent on the presence of IFN-γ. Consistent with this finding, in vivo antibody-mediated protection required IFN-γ and T cells. Together, these data suggest that a close and critical interaction of humoral and cellular immune responses is necessary for providing sterilizing immunity to F. tularensis. Furthermore, serum antibodies conferred protection against lethal respiratory tularemia when given 24 to 48 hr post-exposure and thus this study provides evidence for the use of antibodies for both prophylactic and therapeutic purposes. (This work was supported by NIH Grant PO1 AI056320 (DWM) and UO1 AI057158 (GSK))