Mycobacterium hsp65 DNA entrapped into TDM-loaded PLGA microspheres induces protection in mice against Leishmania (Leishmania) major infection |
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Authors: | Eduardo Antonio Ferraz Coelho Carlos Alberto Pereira Tavares Karla de Melo Lima Célio Lopes Silva José Maciel Rodrigues Jr Ana Paula Fernandes |
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Affiliation: | (1) Sector of Clinical Pathology, COLTEC, Universidade Federal de Minas Gerais, Av. Antônio Carlos, 6627, 31.270-901 Belo Horizonte, Minas Gerais, Brazil;(2) Biological Sciences Institute, Universidade Federal de Minas Gerais, Av. Antônio Carlos, 6627, 31.270-901 Belo Horizonte, Minas Gerais, Brazil;(3) School of Pharmacy, Universidade Federal de Minas Gerais, Av. Antônio Carlos, 6627, 31.270-901 Belo Horizonte, Minas Gerais, Brazil;(4) School of Medicine, Universidade Federal de São Paulo, Av. Bandeirantes, 3900, 1404-900 Ribeirão Preto, São Paulo, Brazil;(5) Nanocore Biotecnologia Ltda., Incubadora Supera, Rua dos Técnicos, s/n, 1404-900 Ribeirão Preto, São Paulo, Brazil |
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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-γ 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. |
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