Abstract
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.
Highlights
Tuberculosis (TB) is an infection caused by Mycobacterium tuberculosis and this disease remains one of the most important causes of death worldwide [1, 2]
The only available vaccine against TB is the attenuated M. bovis Bacillus Calmette-Guerin (BCG) that is recommended by the World Health Organization for all infants under 1 year of age
We previously demonstrated that a DNA plasmid encoding the Mycobacterium leprae 65 kDa heat shock protein exhibited prophylactic [18] and therapeutic activity in a TB murine model [19, 20]
Summary
Tuberculosis (TB) is an infection caused by Mycobacterium tuberculosis and this disease remains one of the most important causes of death worldwide [1, 2]. We previously demonstrated that a DNA plasmid encoding the Mycobacterium leprae 65 kDa heat shock protein exhibited prophylactic [18] and therapeutic activity in a TB murine model [19, 20] In spite of these successful results with homologous vaccination protocols, heterologous prime-boost regimens, capable to increase BCG or rBCG efficiency, are considered more promising for future TB control [11]. In this context, we observed that pVAXhsp and BCG primed neonate mice for a strong immune response to pVAXhsp boosters administered later, at the adult stage [21]. The present study was designed to investigate if a vaccination protocol against TB, using BCG alone or a priming with BCG followed by boosters with pVAXhsp, could aggravate or accelerate experimental autoimmune encephalomyelitis
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