A DISSERTATION SUBMITTED IN PARTIAL FULFILLMENT OF THE REQUIREMENTS FOR THE DEGREE OF MASTERS OF SCIENCE IN ONE HEALTH MOLECULAR BIOLOGY OF SOKOINE UNIVERSITY OF AGRICULTURE. MOROGORO, TANZANIA.Control of East Coast fever (ECF) depends on the use of acaricides against ticks, chemotherapy and vaccination. ECF vaccination is based on an infection and treatment method (ITM), which induces life-long immunity if cattle are exposed to mild tick infestation. However, ECF vaccination has several limitations, such as high cost of simultaneously used antibiotics. The primary objective of this study was to determine whether Toll-like receptor 7(TLR7) agonist could effectively induce strong immunity in calves prior to ECF vaccination and replace the use of long acting tetracycline. Twenty crossbred calves were split into 4 groups; adjuvant (N=10), vaccinated (N=4), infected (N=4) and control (N=2). Stimulation of calves with TLR7 agonist induced a strong innate response in terms of a rapid rise in temperature, skin inflammatory response and pronounced swelling of the lymph node in calves. TLR7-priming induced a significant impact on the response of the calves to subsequent T. parva infection. In comparison to the infected group, lymphocyte counts were higher in calves which received the adjuvant. Furthermore, the combined effect of TLR7 agonist stimulation and T. parva parasite challenge induced a high level of IFN-gamma response almost similar to the response shown by ECF vaccinated calves. Similarly, the adjuvant group attained higher antibody level earlier than the infected control calves. Based on the clinical signs observed from day 14 onwards, calves which received TLR7 agonist developed milder disease signs compared to the infected control calves, which were all treated against ECF on day 18. Only one calf out of ten TLR7-primed calves developed clinical disease signifying a potential adjuvant role of the agonist in ECF vaccination. Possibly the adjuvant acted in this mechanism. This study has demonstrated a practical application TLR7 agonist in ECF vaccination, without simultaneous use of antibiotics.