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Background: Delivery of antigens directly to dendritic cells enhances the immune responses to the antigen and is an attractive approach for eliciting cellular immune responses against mutagenic pathogens like HIV virus. So the aim of this study is evaluation of immune responses elicited by delivered multi-epitopic HIV-1 tat/pol/gag/env recombinant protein to dendritic cells in sito using αDEC205 mAb. Materials and Methods: In this study, recombinant protein expressed by pET23a-HIVtop4 plasmid including HIVtop4 sequence (Gag158-186, Pol150-190, ENV296-323, ENV577-610, Tat1-20 and Tat44-61) in BL21 E. coli cells was used as vaccine model. To exploiting dendritic cells, properties for immunization purposes, we conjugated this recombinant protein chemically to anti body against DEC205 receptor on these cells. Balb/c mice immunized subcutaneously (s.c.) with conjugated multiepitopic protein or un-conjugated one (as control) simultaneously with Poly I: C as dendritic cell maturation factor. Lymphocyte proliferation was measured by bromo di uridine assay, Cytotoxicity by Grenzyme B production activity, IL-4, IL-17, IFN- cytokines production and total antibody by direct and indirect ELISA methods in order. Results: Immunization by anti DEC-205 conjugated peptide led to a significant increase in the proliferative responses of lymphocytes, production of Gr-B, IFN-γ, IL-4 and IL-17 cytokines and total antibody titer in comparison with the none targeted groups. Conclusion: It is concluded that targeting of protein antigens to DEC-205+dendritic cells significantly enhances immune responses in compare to non-targeting strategies. [ABSTRACT FROM AUTHOR]