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Small Ruminant Lentiviruses (SRLV) infect sheep and goats resulting in significant economic losses. This study evaluated for the first time the predicted conformational structure of the SRLV-capsid-protein 25 (SRLV-p25) and analysed the antigenicity of recombinant protein (SRLV-rp25) in mice by coupling to an immunostimulatory complexes based on glycyrrhizinic acid liposomes (GAL) and tested plasma from goats and sheep naturally infected. Analysis in silico and conformational structure of SRLV-p25 (genotype B-FESC-752) showed similar characteristics to other lentiviral capsids. Efficient expression of SRLV-rp25 was confirmed by Western Blot. The humoral immune responses in mice showed an increased level of antibodies from day 21 to 35 of the SRLV-rp25-GAL and SRLV-rp25-ISCOM® groups and the cellular immune response showed no significant difference in IL-10 levels (P > 0.05), however a significant difference (P < 0.001) was observed when comparing SRLV-rp25-GAL with SRLV-rp25 groups. Immunoreactivity towards SRLV-rp25 revealed 61% of positive samples from naturally infected goats and sheep.