Abstract
Despite substantial efforts in recent years toward the development of new vaccines and drugs against tuberculosis (TB), success has remained elusive. Immunotherapy of TB with mycobacterial Hsp65 as a DNA vaccine (DNA-hsp65) results in a reduction of systemic bacterial loads and lung tissue damage, but the high homology of Hsp65 with the mammalian protein raises concern that pathological autoimmune responses may also be triggered. We searched for autoimmune responses elicited by DNA-hsp65 immunotherapy in mice chronically infected with TB by evaluating the humoral immune response and comprehensive histopathology using stereology. Cross-reactive antibodies between mycobacterial and mammalian Hsp60/65 were detected; however, no signs of pathological autoimmunity were found up to 60 days after the end of the therapy.
Keywords:
DNA vaccine; autoimmune response; heat-shock protein; immunotherapy; tuberculosis.
Publication types
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Research Support, Non-U.S. Gov't
MeSH terms
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Animals
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Antibodies, Bacterial / immunology*
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Autoimmunity / drug effects
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Autoimmunity / immunology*
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Bacterial Proteins / administration & dosage
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Bacterial Proteins / immunology*
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Chaperonin 60 / administration & dosage
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Chaperonin 60 / antagonists & inhibitors
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Chaperonin 60 / immunology*
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Cross Reactions / drug effects
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Cross Reactions / immunology
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Immunity, Humoral / drug effects
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Immunity, Humoral / immunology
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Immunotherapy / methods
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Mice
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Mice, Inbred BALB C
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Mitochondrial Proteins / antagonists & inhibitors
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Mitochondrial Proteins / immunology*
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Mycobacterium leprae / immunology*
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Tuberculosis Vaccines / administration & dosage
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Tuberculosis Vaccines / immunology
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Vaccines, DNA / administration & dosage
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Vaccines, DNA / immunology*
Substances
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Antibodies, Bacterial
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Bacterial Proteins
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Chaperonin 60
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Hspd1 protein, mouse
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Mitochondrial Proteins
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Tuberculosis Vaccines
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Vaccines, DNA
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heat-shock protein 65, Mycobacterium