This longitudinal study was performed for field trial of heterologous vaccine strains of lumpy skin disease (LSD) to provide details on the characteristics of induced immune responses by measurement of specific antibody and target cytokines – critical parameters in immune response that can be related to the durability of protection. The experimental calves were vaccinated with Gorgan-GPV and RM/65-SPV vaccines and humoral and cellular immunity were evaluated weekly. In each vaccinated groups, cross-neutralising antibody titers against LSD virus (LSDV) could be detected, and this rate in GGPV-vaccinated calves (GC) was higher than RSPV-vaccinated calves (RC) in all weeks of experiments. The stimulation index and IFN-γ and IL-4 production in response to homologous virus were higher than to the heterologous virus in all time points. The highest difference between them was observed in RVC, and a significant difference were only shown at 21-day post vaccination (DPV) (p<0.001). The results of this study indicated that GGPV-vaccine had a good immunogenic response due to induction of high antibody titre and higher lymphocyte proliferation and IFN-γ and IL-4 production. Therefore, it was considered suitable to control LSD.