title: Immunotherapy of tuberculosis with Mycobacterium leprae Hsp65 as a DNA vaccine triggers cross-reactive antibodies against mammalian Hsp60 but not pathological autoimmunity.
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.
authors.affiliation: The Centre for Tuberculosis Research; Department of Biochemistry and Immunology; Ribeirão Preto School of Medicine; University of São Paulo; São Paulo, Brazil.
authors.forename: Nayara T S
authors.initials: NT
authors.lastname: Doimo
authors.affiliation: The Centre for Tuberculosis Research; Department of Biochemistry and Immunology; Ribeirão Preto School of Medicine; University of São Paulo; São Paulo, Brazil.
authors.forename: Carlos R
authors.initials: CR
authors.lastname: Zárate-Bladés
authors.affiliation: The Centre for Tuberculosis Research; Department of Biochemistry and Immunology; Ribeirão Preto School of Medicine; University of São Paulo; São Paulo, Brazil.
authors.forename: Rodrigo F
authors.initials: RF
authors.lastname: Rodrigues
authors.affiliation: Department of Pathology; Ribeirão Preto School of Medicine; University of São Paulo; São Paulo, Brazil.
authors.forename: Cristiane
authors.initials: C
authors.lastname: Tefé-Silva
authors.affiliation: Veterinary Medical Department of Anatomical Pathology; State University of Rio de Janeiro; Rio de Janeiro, Brazil.
authors.forename: Marcele N S
authors.initials: MN
authors.lastname: Trotte
authors.affiliation: The Centre for Tuberculosis Research; Department of Biochemistry and Immunology; Ribeirão Preto School of Medicine; University of São Paulo; São Paulo, Brazil.
authors.forename: Patrícia R M
authors.initials: PR
authors.lastname: Souza
authors.affiliation: The Centre for Tuberculosis Research; Department of Biochemistry and Immunology; Ribeirão Preto School of Medicine; University of São Paulo; São Paulo, Brazil.
authors.forename: Luana S
authors.initials: LS
authors.lastname: Soares
authors.affiliation: The Centre for Tuberculosis Research; Department of Biochemistry and Immunology; Ribeirão Preto School of Medicine; University of São Paulo; São Paulo, Brazil.
authors.forename: Wendy M
authors.initials: WM
authors.lastname: Rios
authors.affiliation: Department of Pathology; Ribeirão Preto School of Medicine; University of São Paulo; São Paulo, Brazil.
authors.forename: Elaine M
authors.initials: EM
authors.lastname: Floriano
authors.affiliation: The Centre for Tuberculosis Research; Department of Biochemistry and Immunology; Ribeirão Preto School of Medicine; University of São Paulo; São Paulo, Brazil.
authors.forename: Izaira T
authors.initials: IT
authors.lastname: Brandão
authors.affiliation: The Centre for Tuberculosis Research; Department of Biochemistry and Immunology; Ribeirão Preto School of Medicine; University of São Paulo; São Paulo, Brazil.
authors.forename: Ana P
authors.initials: AP
authors.lastname: Masson
authors.affiliation: Laboratory of Immunology; Heart Institute (InCor); School of Medicine; University of São Paulo; São Paulo, Brazil; Institute for Investigation in Immunology (iii)-National Institute of Science and Technology; São Paulo, Brazil.
authors.forename: Verônica
authors.initials: V
authors.lastname: Coelho
authors.affiliation: Department of Pathology; Ribeirão Preto School of Medicine; University of São Paulo; São Paulo, Brazil.
authors.forename: Simone G
authors.initials: SG
authors.lastname: Ramos
authors.affiliation: The Centre for Tuberculosis Research; Department of Biochemistry and Immunology; Ribeirão Preto School of Medicine; University of São Paulo; São Paulo, Brazil.
authors.forename: Celio L
authors.initials: CL
authors.lastname: Silva
mesh_terms: D000818:Animals; D000907:Antibodies, Bacterial / Q000276:immunology*; D015551:Autoimmunity / Q000187:drug effects / Q000276:immunology*; D001426:Bacterial Proteins / Q000008:administration & dosage / Q000276:immunology*; D018834:Chaperonin 60 / Q000008:administration & dosage / Q000037:antagonists & inhibitors / Q000276:immunology*; D003429:Cross Reactions / Q000187:drug effects / Q000276:immunology; D056724:Immunity, Humoral / Q000187:drug effects / Q000276:immunology; D007167:Immunotherapy / Q000379:methods; D051379:Mice; D008807:Mice, Inbred BALB C; D024101:Mitochondrial Proteins / Q000037:antagonists & inhibitors / Q000276:immunology*; D009166:Mycobacterium leprae / Q000276:immunology*; D032581:Tuberculosis Vaccines / Q000008:administration & dosage / Q000276:immunology; D019444:Vaccines, DNA / Q000008:administration & dosage / Q000276:immunology*
chemical_list: D000907:Antibodies, Bacterial; D001426:Bacterial Proteins; D018834:Chaperonin 60; C557066:Hspd1 protein, mouse; D024101:Mitochondrial Proteins; D032581:Tuberculosis Vaccines; D019444:Vaccines, DNA; C074119:heat-shock protein 65, Mycobacterium
keywords: DNA vaccine; autoimmune response; heat-shock protein; immunotherapy; tuberculosis