The results of this study provide the first evidence that two complete
ly separate vaccine approaches, one based on a subunit vaccine consist
ing of a mild adjuvant admired with purified culture filtrate proteins
and enhanced by the cytokine interleukin-2 and the second based on im
munization with DNA encoding the Ag85A protein secreted by Mycobacteri
um tuberculosis, could both prevent the onset of caseating disease, wh
ich is the hallmark of the guinea pig aerogenic infection model. In bo
th cases, however, the survival of vaccinated guinea pigs was shorter
than that conferred by Mycobacterium bovis BCG, with observed mortalit
y of these animals probably due to consolidation of lung tissues by ly
mphocytic granulomas. An additional characteristic of these approaches
was that neither induced skin test reactivity to commercial tuberculi
n. These data thus provide optimism that development of nonliving vacc
ines which can generate long-lived immunity approaching that conferred
by the BCG vaccine is a feasible goal.