A prime-boost strategy conserving BCG is considered the most promising vaccine to control tuberculosis. A boost with a DNA vaccine containing the mycobacterial gene of a heat shock protein (pVAXhsp65) after BCG priming protected mice against experimental tuberculosis. However, anti-hsp65 immunity could worsen an autoimmune disease due to molecular mimicry. In this investigation, we evaluated the effect of a previous BCG or BCG/pVAXhsp65 immunization on experimental autoimmune encephalomyelitis (EAE) development. Female Lewis rats were immunized with BCG or BCG followed by pVAXhsp65 boosters. The animals underwent EAE induction and were daily evaluated for weight loss and clinical score. They were euthanized during recovery phase to assess immune response and inflammatory infiltration at the central nervous system. Previous immunization did not aggravate or accelerate clinical score or weight loss. In addition, this procedure clearly decreased inflammation in the brain. BCG immunization modulated the host immune response by triggering a significant reduction in IL-10 and IFN-γ levels induced by myelin basic protein. These data indicated that vaccination protocols with BCG or BCG followed by boosters with pVAXhsp65 did not trigger a deleterious effect on EAE evolution. 1. Introduction Tuberculosis (TB) is an infection caused by Mycobacterium tuberculosis and this disease remains one of the most important causes of death worldwide [1, 2]. Factors as coinfection with human immunodeficiency virus and emergence of drug resistance in M. tuberculosis strains have hampered TB control [3, 4]. The only available vaccine against TB is the attenuated M. bovis Bacillus Calmette-Guérin (BCG) that is recommended by the World Health Organization for all infants under 1 year of age. Around 100 million newborn children receive this vaccine and the global vaccine coverage is estimated to be 80% [5, 6]. In spite of this extensive use, numerous well-documented trials showed significant variation, from 0 to 80%, in BCG protective efficacy [7]. This has been attributed to variability in BCG vaccine strains and environmental factors as well as host genetic background [8, 9]. Although BCG seems to provide protection against disseminated tuberculosis in newborns and children, the induced immunity wanes with age, resulting in insufficient protection against adult pulmonary TB [10, 11]. In this context, there is a great interest in the development of new vaccines against TB. Numerous alternative living and nonliving putative TB vaccines are being lately tested [12–14]. Experimental
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