Mycobacterium hsp65 DNA entrapped into TDM-loaded PLGA microspheres induces protection in mice against Leishmania (Leishmania) major infection.
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.
Coelho
Eduardo Antonio Ferraz
EA
Sector of Clinical Pathology, COLTEC, Universidade Federal de Minas Gerais, Av. Antônio Carlos, 6627, 31.270-901, Belo Horizonte, Minas Gerais, Brazil.
Tavares
Carlos Alberto Pereira
CA
Lima
Karla de Melo
Kde M
Silva
Célio Lopes
CL
Rodrigues
José Maciel
JM
Fernandes
Ana Paula
AP
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*
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