Mycobacterium hsp65 DNA entrapped into TDM-loaded PLGA microspheres induces protection in mice against Leishmania (Leishmania) major infection

• Published in: Parasitology research (1987) 2006-05, Vol.98 (6), p.568-575
• Main Authors: FERRAZ COELHO, Eduardo Antonio, PEREIRA TAVARES, Carlos Alberto, DE MELO LIMA, Karla, SILVA, Célio Lopes, RODRIGUES, José Maciel, FERNANDES, Ana Paula
• Format: Article
• Language: English
• Subjects: Animals; Antibodies, Protozoan - blood; Bacterial Proteins - genetics; Bacterial Proteins - immunology; Biological and medical sciences; Chaperonin 60; Chaperonins - genetics; Chaperonins - immunology; Cord Factors - immunology; Cytokines - biosynthesis; Edema - prevention & control; Enzyme-Linked Immunosorbent Assay; Female; Fundamental and applied biological sciences. Psychology; General aspects; General aspects and techniques. Study of several systematic groups. Models; Immunoglobulin G - blood; Invertebrates; Leishmania major - immunology; Leishmaniasis, Cutaneous - immunology; Leishmaniasis, Cutaneous - prevention & control; Lower Extremity - parasitology; Lower Extremity - pathology; Lymphocytes - immunology; Mice; Mice, Inbred BALB C; Microspheres; Mycobacterium tuberculosis; Protozoan Vaccines - immunology; Spleen; Vaccines, DNA - immunology
• ISSN: 0932-0113; 1432-1955
• DOI: 10.1007/s00436-005-0088-5

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.