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Vaccination with Mtb72F formulated in AS02A (Mtb72F+AS02A) or Mtb72F formulated in AS01B (Mtb72F+AS01B) was protective against central nervous system (CNS) challenge with<jats:italic>Mycobacterium tuberculosis<\/jats:italic>H37Rv to an extent comparable to that of vaccination with BCG. Similar accelerated clearances of bacilli from the cerebrospinal fluid, reduced leukocytosis, and less pathology of the brain and lungs were noted. Weight loss of infected rabbits was less extensive for Mtb72F+AS02A-vaccinated rabbits. In addition, protection against<jats:italic>M. tuberculosis<\/jats:italic>H37Rv CNS infection afforded by BCG\/Mtb72F in a prime-boost strategy was similar to that by BCG alone. 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