Mechanism of the protective immunity against murine typhoid: persistence of salmonella L forms in the liver after immunization with live‐cell vaccines

Live‐cell vaccines of Salmonella typhimurium, either a sub‐lethal dose of a wild‐type (strain LT2) or a high dose of its two‐heptose Rd1 mutant (strain SL1004), induced acquired resistance to murine typhoid, which remained 180 days after immunozation. Growth of S. typhimurium as a bacillary form ceased between days 30 and 60 of immunization, but L forms of this bacterium colonized the liver (the mean number of L forms in the liver: 600 L‐forming units) even at 180 days post‐immunization. In contrast, a high inoculum of either a Ra mutant (strain TV148) of strain LT2 or S. schottmülleri 8006 sharing the same O antigenic components with those of S. typhimurium induced only a short‐lived protection in proportion to the number of L forms in the liver, and the protective immunity was lost before day 180. However, there was no significant difference in the salmonella‐specific T‐cell responses among groups of immunized mice on day 180 of immunization. A lethal infection with strain LT2 in mice which had been immunized 75 days previously with living cells of strain SL1004 resulted in a rapid clearance of the challenge inoculum, together with a rapid elevation of anti‐S. typhimurium antibody responses. Thus, the present data suggest that the long‐lived immunity conferred upon live S. typhimurium vaccines is attributable to the colonization of this bacterium in the liver as L forms and the ability to colonize the liver as L forms is independent of the brain length of salmonella O‐antigens.