title: Mycobacterium hsp65 DNA entrapped into TDM-loaded PLGA microspheres induces protection in mice against Leishmania (Leishmania) major infection.
abstract: Heat shock proteins (HSPs) are highly conserved among different organisms. A mycobacterial HSP65 DNA vaccine was previously shown to have prophylactic and immunotherapeutic effects against Mycobacterium tuberculosis infection in mice. Here, BALB/c mice were immunized with mycobacterial DNA-hsp65 or with DNA-hsp65 and trehalose dymicolate (TDM), both carried by biodegradable microspheres (MHSP/TDM), and challenged with Leishmania (Leishmania) major. MHSP/TDM conferred protection against L. major infection, as indicated by a significant reduction of edema and parasite loads in infected tissues. Although high levels of interferon-gamma and low levels of interleukin (IL)-4 and IL-10 were detected in mice immunized with DNA-hsp65 or MHSP/TDM, only animals immunized with MHSP/TDM displayed a consistent Th1 immune response, i.e., significantly higher levels of anti-soluble Leishmania antigen (SLA) immunoglobulin G (IgG)2a and low anti-SLA IgG1 antibodies. These findings indicate that encapsulated MHSP/TDM is more immunogenic than naked hsp65 DNA, and has great potential to improve vaccine effectiveness against leishmaniasis and tuberculosis.
authors.affiliation: Sector of Clinical Pathology, COLTEC, Universidade Federal de Minas Gerais, Av. Antônio Carlos, 6627, 31.270-901, Belo Horizonte, Minas Gerais, Brazil.
authors.forename: Eduardo Antonio Ferraz
authors.initials: EA
authors.lastname: Coelho
authors.forename: Carlos Alberto Pereira
authors.initials: CA
authors.lastname: Tavares
authors.forename: Karla de Melo
authors.initials: Kde M
authors.lastname: Lima
authors.forename: Célio Lopes
authors.initials: CL
authors.lastname: Silva
authors.forename: José Maciel
authors.initials: JM
authors.lastname: Rodrigues
authors.forename: Ana Paula
authors.initials: AP
authors.lastname: Fernandes
mesh_terms: D000818:Animals; D000913:Antibodies, Protozoan / Q000097:blood; D001426:Bacterial Proteins / Q000235:genetics* / Q000276:immunology*; D018834:Chaperonin 60; D018833:Chaperonins / Q000235:genetics* / Q000276:immunology*; D003311:Cord Factors / Q000276:immunology; D016207:Cytokines / Q000096:biosynthesis; D004487:Edema / Q000517:prevention & control; D004797:Enzyme-Linked Immunosorbent Assay; D005260:Female; D007074:Immunoglobulin G / Q000097:blood; D018320:Leishmania major / Q000276:immunology*; D016773:Leishmaniasis, Cutaneous / Q000276:immunology / Q000517:prevention & control*; D035002:Lower Extremity / Q000469:parasitology / Q000473:pathology; D008214:Lymphocytes / Q000276:immunology; D051379:Mice; D008807:Mice, Inbred BALB C; D008863:Microspheres; D009169:Mycobacterium tuberculosis; D016052:Protozoan Vaccines / Q000276:immunology*; D013154:Spleen; D019444:Vaccines, DNA / Q000276:immunology*
chemical_list: D000913:Antibodies, Protozoan; D001426:Bacterial Proteins; D018834:Chaperonin 60; D003311:Cord Factors; D016207:Cytokines; D007074:Immunoglobulin G; D016052:Protozoan Vaccines; D019444:Vaccines, DNA; C074119:heat-shock protein 65, Mycobacterium; D018833:Chaperonins