DIFFERENTIAL RESPONSES TO CHALLENGE WITH LIVE AND DEAD MYCOBACTERIUM-BOVIS BACILLUS-CALMETTE-GUERIN

Bacillus Calmette-Guerin (BCG) vaccination has been shown to protect a gainst challenge with virulent Mycobacterium tuberculosis in a range o f experimental animal models: in each case, protective efficacy requir es vaccination with live bacteria. With the goal of moving to a new ge neration of safer, nonliving vaccines, efforts have been made to ident ify the factors that determine the efficacy of live vaccination. We sh ow that injection of live, but not dead, BCG induces localized swellin g in the mouse footpad model. Live and dead bacteria induce similar re sponses during the first week after vaccination as determined by immun ohistochemical analysis of the site of injection and of the draining l ymph node. The subsequent differential response is characterized by mi gration of acid-fast bacilli to the draining lymph node in the case of the live vaccine. This is accompanied by an increase in mononuclear c ells in the lymph node and by expression of inducible nitric oxide syn thase (iNOS) both in the lymph node and at the site of injection. The ability of the bacteria to migrate to the lymph node may be an importa nt element in the efficacy of live BCG vaccination.