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Int Immunopharmacol ; 59: 97-105, 2018 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-29649772

RESUMO

Recombinant cysteine peptidase vaccine can induce protective immunity against cutaneous leishmaniasis. However, the antigenic diversity and variable immunogenicity prevents them from being approved for general vaccination. Different approaches like adjuvant application and antigen delivery systems are studied to increase their efficacy. Nanoparticles can both stimulated antigen uptakes and affect direction of immune response. In this study the effect of PLGA nanoparticles were considered to enhance the immune response against recombinant CPA (CPA) and CPB (CPB). For this purpose, L. major CPA and CPB were prepared. PLGA were conjugated to the proteins using Aldehyde/Hydrazine Reaction. Conjugation efficacy and created nanoparticle morphology were determined by FTIR and SEM methods, respectively. BALB/c mice were received intraperitoneally three boosts of 7 µg/mouse of each antigen alone (CPA/CPB/CPA + CPB) or as PLGA conjugated form in different Study groups, at 3 weeks interval. After vaccination, mice were challenged with 106L. major, subcutaneously. Time course study of lesion development demonstrated nanoparticle efficacy in parasite dissemination control that confirmed by spleen parasite burden assay. Significant induction of nitric oxide production by peritoneal macrophages and increase in splenocyte IFN-γ production showed the protective effect of PLGA-CPA/CPB vaccination in comparison to CPA and CPB alone. Current study demonstrated that the conjugation of the antigen with the PLGA can activate immune responses against L. major. However, further study is necessary to assess the long-term effect and other aspects of immune response.


Assuntos
Adjuvantes Imunológicos/uso terapêutico , Cisteína Proteases/uso terapêutico , Ácido Láctico/uso terapêutico , Vacinas contra Leishmaniose , Leishmaniose Cutânea/tratamento farmacológico , Nanopartículas/uso terapêutico , Ácido Poliglicólico/uso terapêutico , Adjuvantes Imunológicos/química , Animais , Cisteína Proteases/química , Feminino , Interferon gama/imunologia , Interleucina-4/imunologia , Ácido Láctico/química , Leishmania , Leishmaniose Cutânea/parasitologia , Macrófagos Peritoneais/efeitos dos fármacos , Macrófagos Peritoneais/metabolismo , Camundongos Endogâmicos BALB C , Nanopartículas/química , Óxido Nítrico/metabolismo , Carga Parasitária , Ácido Poliglicólico/química , Copolímero de Ácido Poliláctico e Ácido Poliglicólico , Baço/efeitos dos fármacos , Baço/imunologia , Baço/parasitologia , Células Th1/imunologia
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