cord-factors and Edema

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.

Topics: Animals; Antibodies, Protozoan; Bacterial Proteins; Chaperonin 60; Chaperonins; Cord Factors; Cytokines; Edema; Enzyme-Linked Immunosorbent Assay; Female; Immunoglobulin G; Leishmania major; Leishmaniasis, Cutaneous; Lower Extremity; Lymphocytes; Mice; Mice, Inbred BALB C; Microspheres; Mycobacterium tuberculosis; Protozoan Vaccines; Spleen; Vaccines, DNA