Paracoccidioidomycosis vaccine.
Paracoccidioidomycosis is a granulomatous pulmonary infection that is generally controlled by chemotherapy. The efficacy of treatment, however, is limited by the status of the host immune response. The inhibition of a Th-2 immunity or the stimulation of Th-1 cytokines generally increases the efficacy of antifungal drugs. ( 1) This has been achieved by immunization with an internal peptide of the major diagnostic antigen gp43 of Paracoccidioides brasiliensis. Peptide 10 (QTLIAIHTLAIRYAN) elicits an IFN-γ rich Th-1 immune response that protects against experimental intratracheal infection by this fungus. The combination of chemotherapy with P10 immunization showed additive protective effect even after 30 d of infection or in anergic mice, rendering in general, increased production of IL-12 and IFN-γ and reduction of IL-4 and IL-10. Immunotherapy with P10 even in the absence of simultaneous chemotherapy has been effective using various protocols, adjuvants, nanoparticles, P10-primed dendritic cells, and especially a combination of plasmids encoding the P10 minigene and IL-12. Gene therapy, in a long-term infection protocol succeeded in the virtual elimination of the fungus, preserving the lung structure, free from immunopathological side effects.
Cell Biology Division, Department of Microbiology, Federal University of São Paulo, São Paulo, Brazil. travassos@unifesp.br
Luiz R
LR
Travassos
Carlos P
CP
Taborda
D000951:Antigens, Neoplasm / Q000378:metabolism; D006023:Glycoproteins / Q000138:chemical synthesis; D006801:Humans; D007167:Immunotherapy / Q000379:methods*; D007371:Interferon-gamma / Q000378:metabolism; D016753:Interleukin-10 / Q000378:metabolism; D018664:Interleukin-12 / Q000378:metabolism; D015847:Interleukin-4 / Q000378:metabolism; D010229:Paracoccidioidomycosis / Q000276:immunology / Q000517:prevention & control* / Q000628:therapy*; D010446:Peptide Fragments / Q000138:chemical synthesis; D019444:Vaccines, DNA / Q000627:therapeutic use
D000951:Antigens, Neoplasm; D006023:Glycoproteins; C550731:P10 peptide, Paracoccidioides brasiliensis; D010446:Peptide Fragments; D019444:Vaccines, DNA; C107095:tumor-associated antigen, gp43; D016753:Interleukin-10; D018664:Interleukin-12; D015847:Interleukin-4; D007371:Interferon-gamma