EXPRESSION OF THE YERSINIA-PESTIS CAPSULAR ANTIGEN (F1 ANTIGEN) ON THE SURFACE OF AN AROA MUTANT OF SALMONELLA-TYPHIMURIUM INDUCES HIGH-LEVELS OF PROTECTION AGAINST PLAGUE

The caf operon from Yersinia pestis encoding the structural subunit (c af1), the molecular chaperone (caf1M), the outer membrane anchor (caf1 A), and the regulatory protein (caf1R) was cloned into Salmonella typh imurium SL3261 aroA. The recombinant Salmonella organisms were encapsu lated when cultured at 37 degrees C but not when cultured at 28 degree s C. Oral inoculation of mice with the recombinant Salmonella induced predominantly an immunoglobulin G2a response to F1 antigen, and isolat ed T cells showed a recall response to soluble or Salmonella-associate d F1 antigen. Mice immunized with S. typhimurium SL3261 aroA expressin g F1 antigen intracellularly developed lower antibody responses to F1 antigen and showed a T-cell recall response only to Salmonella-associa ted F1 antigen. Mice immunized orally with two doses of the recombinan t Salmonella which expressed F1 antigen on the surface were protected against 10(7) 50% lethal doses (LD50) of virulent Y. pestis given by t he subcutaneous route of challenge, whereas mice immunized dth the rec ombinant Salmonella expressing F1 antigen intracellularly were only pa rtially protected against 10(5) LD50 of Y. pestis.