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Background: Several approaches have not been successful to suppress HIV (Human immunodeficiency virus) infection among infected individuals or to prevent it yet. In order to expand strong HIV specific humoral and cellular responses, Virus-like particles (VLPs) as potential vaccines show significant increase in neutralizing antibodies secretion, T-cell count and also secretion of cytokines. Objective: This study aimed at immunological evaluation of VLPs harboring high copy of MPERV3 in BALB/c mice. Methods: Female BALB/c mice were immunized with homologous and heterologous primeboosting regimens of HIV-1 VLPMPER-V3. Their immune responses were evaluated for humoral responses (Total IgG and IgG isotyping) and cellular responses (IFN-γ, IL-5 secretion, in vitro CTL assay and T cell proliferation) and compared in immunized mice. Results: The data showed robust induction of humoral response in mice groups which received different regimens of VLP. Furthermore, analysis of cytokine profile indicated that the highest IL-5 secretion was related to VLP+M50 group and confirmed the dominance of Th2 immunity in this group. Conclusion: This study showed that VLP MPER-V3 as a potential vaccine candidate has the potency as an effective prophylactic vaccine and this finding guarantees further investigations to achieve a promising HIV-1 vaccine candidate.