Therapeutic efficacy of ‘Indigenous vaccine’ developed from highly pathogenic ‘Indian Bison Type native goat adapted’ biotype of Mycobacterium avium subspecies paratuberculosis (MAP) was evaluated in naturally infected Patanwadi breed of sheep flock located at Livestock Research Station (LRS), Sardarkrushinagar, Dantiwada in North Gujarat. Fifty Johne’s disease positive (by microscopy, PCR and ELISA), ready to cull, weak and discarded adult sheep were randomly divided into 2 groups viz., ‘Vaccinated’ (N = 35) and ‘Control’ (N = 15). After vaccination sheep were monitored for physical condition, clinical symptoms (weakness and diarrhea), morbidity, mortality, body weights, shedding of MAP in feces and humoral immune responses upto 120 days at 30 days intervals. Average body weights gained were significantly higher (P<0.01) in ‘Vaccinated group’ as compared to ‘Control group’. No mortality was observed in the vaccinated group during the study period. Shedding of MAP in feces was reduced in vaccinated sheep by 17.15% whereas shedding increased in control sheep. Vaccinated sheep had significantly higher (P<0.01) antibody titer against MAP infection in comparison to ‘Control’ sheep. Sheep positive on 0 DPV in fecal PCR and blood PCR were found negative on 120 DPV. ‘Indigenous vaccine’ effectively restricted MAP infection and improved immunity of the sheep flock exhibiting symptoms of clinical Johne’s disease.