作者: Wowk, Pryscilla Fanini ; Franco, Luís Henrique ; Paula, Marina Oliveira ; Fonseca, Denise Morais da ; Elói-Santos, Silvana Maria ; Wendling, Ana Paula ; Palaci, Moisés ; Teixeira-Carvalho, Andréa ; Bonato, Vânia Luiza Deperon ; Silva, Flávia Dias Coelho ; Vianna, Élcio dos Santos Oliveira ; Silva, Célio Lopes ; Martins-Filho, Olindo Assis ; Augusto, Valéria Maria ; Vinhas, Solange Alves

Previously we showed that 65-kDa Mycobacterium leprae heat shock protein (Hsp65) is a target for the development of a tuberculosis vaccine. Here we evaluated peripheral blood mononuclear cells (PBMC) from healthy individuals or tuberculosis patients stimulated with two forms of Hsp65 antigen, recombinant DNA that encodes Hsp65 (DNA-HSP65) or recombinant Hsp65 protein (rHsp65) in attempting to mimic a prophylactic or therapeutic study in vitro, respectively. Proliferation and cytokine-producing CD4⁺ or CD8⁺ cell were assessed by flow cytometry. The CD4⁺ cell proliferation from healthy individuals was stimulated by DNA-HSP65 and rHsp65, while CD8⁺ cell proliferation from healthy individuals or tuberculosis patients was stimulated by rHSP65. DNA-HSP65 did not improve the frequency of IFN-gamma⁺ cells from healthy individuals or tuberculosis patients. Furthermore, we found an increase in the frequency of IL-10-producing cells in both groups. These findings show that Hsp65 antigen activates human lymphocytes and plays an immune regulatory role that should be addressed as an additional antigen for the development of antigen-combined therapies.

2013-06-01·Mycopathologia3区 · 生物学

DNA-hsp65 Vaccine as Therapeutic Strategy to Treat Experimental Chromoblastomycosis Caused by Fonsecaea Pedrosoi

3区 · 生物学

Article

作者: Márcio Souza Jerônimo ; Yanna Karla de Medeiros Nóbrega ; Florêncio Figueiredo Cavalcante Neto ; Ana Camila Oliveira Souza ; Célio Lopes Silva ; Alice Melo Ribeiro ; Isaque Medeiros Siqueira ; Anamélia Lorenzetti Bocca ; Maria Sueli Soares Felipe ; Karina Smidt Simon

Chromoblastomycosis (CBM) is a chronic subcutaneous mycosis, caused by several dimorphic, pigmented dematiaceous fungi. Patients with the disease are still considered a therapeutic challenge, mainly due to its recalcitrant nature. There is no "gold standard" treatment for this neglected mycosis, but rather there are several treatment options. Chemotherapy alternatives include 5-flucytosine, itraconazole, terbinafine, fluconazole, thiabendazole, ketoconazole and amphotericin B, although the healing of severe cases is still uncommon. However, several studies have reported the DNA vaccine to be promising in the treatment for fungal infections; this vaccine allows the host to restore depressed cellular immunity, minimizing the toxic effects from conventional antifungal therapies. This work was therefore carried out aiming to establish a suitable model for experimental CBM, suggesting also new therapies, including DNA-hsp65 vaccine. By analyzing the morphometrical and histopathological aspects and by quantifying the fungal burden, the results showed the establishment of a chronic, although transitory, experimental CBM model with lesions similar to those presented in humans. A treatment regimen using intralesional itraconazole or amphotericin B was effective in treating experimental CBM, as was a therapy using naked DNA-hsp65 vaccine. It has also been shown that chemotherapy associated with DNA-hsp65 vaccine is promising in the treatment for CBM.

2013-03-18·Human Vaccines & Immunotherapeutics3区 · 医学

Novel therapeutic vaccines [(HSP65 + IL-12)DNA-, granulysin- and Ksp37-vaccine] against tuberculosis and synergistic effects in the combination with chemotherapy

3区 · 医学

Article

作者: Hitoshi Nakatani ; Esterlina V. Tan ; Satomi Hashimoto ; Masaji Okada ; Noriko Kanamaru ; Yasuko Nishida ; Yasushi Takamori ; Marjorie L. Cang ; Paul Saunderson ; Yasuhumi Kaneda ; Toshihiro Nakajima ; Shiho Nishimatsu ; Yoko Kita ; E.C. Dela Cruz ; David McMurray

PURPOSEMulti-drug resistant tuberculosis (MDR-TB) and extremely drug resistant (XDR) TB are big problems in the world. We have developed novel TB therapeutic vaccines, HVJ-Envelope/HSP65 + IL-12 DNA vaccine (HSP65-vaccine), granulysin vaccine and killer specific secretory protein of 37kDa (Ksp37) vaccine.METHODS AND RESULTSHSP65 vaccine showed strong therapeutic effect against both MDR-TB and XDR-TB in mice. Intradermal immunization of HSP65-vaccine showed stronger therapeutic effect against TB than intramuscular or subcutaneous immunization. Furthermore, the synergistic therapeutic effect was observed when the vaccine was administrated in combination with Isoniazid (INH), which is a first line drug for chemotherapy. The combination of types of vaccines (HSP65- and granulysin- vaccines) also showed synergistic therapeutic effect. In the monkey model, granulysin-vaccine prolonged the survival period after the infection of TB and long-term survival was observed in vaccine-treated group. We examined the potential of two kinds of novel DNA vaccines (Ksp37-vaccine and granulysin-vaccine). Both vaccines augmented in vivo differentiation of CTL against TB. We measured the amount of Ksp37 protein in human serum and revealed that the level of Ksp37 protein of patients with tuberculosis was lower than that of healthy volunteers. Therefore, we established Ksp37 transgenic mice as well as granulysin transgenic mice to elucidate the function of those proteins. Both transgenic mice were resistant to TB infection.CONCLUSIONThese data indicate the potential of combinational therapy; the combination of two DNA vaccines or combination of DNA vaccine with antibiotic drug. Thus, it will provide a novel strategy for the treatment of MDR-TB.

100 项与 DNA-HSP65 相关的药物交易

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