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Front Immunol ; 9: 18, 2018.
Artigo em Inglês | MEDLINE | ID: mdl-29441060

RESUMO

Despite advances, identification and formulation of safe and effective vaccine for long-lasting protection against leishmaniasis is still inadequate. In this study, we have identified a novel antigen, leishmanial elongation factor-1α (EF1-α), as an immunodominant component of solubilized leishmanial membrane antigens that reacts with visceral leishmaniasis (VL) sera and induces cellular proliferative and cytokine response in PBMCs of cured VL subjects. Leishmanial EF1-α is a 50 kDa antigen that plays a crucial role in pathogen survival by regulating oxidative burst in the host phagocytes. Previously, immunodominant truncated forms of EF1-α from different species of Leishmania have been reported. Formulation of the L. donovani 36 kDa truncated as well as the cloned recombinant EF1-α in cationic liposomes induce strong resistance to parasitic burden in liver and spleen of BALB/c mice through induction of DTH and a IL-10 and TGF-ß suppressed mixed Th1/Th2 cytokine responses. Multiparametric analysis of splenocytes for generation of antigen-specific IFN-γ, IL2, and TNF-α producing lymphocytes indicate that cationic liposome facilitates expansion of both CD4+ as well as CD8+ memory and effector T cells. Liposomal EF1-α is a novel and potent vaccine formulation against VL that imparts long-term protective responses. Moreover, the flexibility of this formulation opens up the scope to combine additional adjuvants and epitope selected antigens for use in other disease forms also.


Assuntos
Anticorpos Antiprotozoários/imunologia , Antígenos de Protozoários/imunologia , Leishmania donovani/imunologia , Leishmaniose Visceral/prevenção & controle , Fator 1 de Elongação de Peptídeos/imunologia , Vacinas Protozoárias/imunologia , Animais , Linfócitos T CD8-Positivos/imunologia , Humanos , Memória Imunológica/imunologia , Interleucina-10/imunologia , Leishmaniose Visceral/imunologia , Fígado/parasitologia , Proteínas de Membrana/imunologia , Camundongos , Camundongos Endogâmicos BALB C , Fagócitos/imunologia , Explosão Respiratória/imunologia , Baço/parasitologia , Células Th1/imunologia , Células Th2/imunologia , Fator de Crescimento Transformador beta1/imunologia
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