Randomized field trial of a therapeutic vaccine against Trypanosoma cruzi natural infection in dogs and correlates for efficacy

Chagas disease, caused by Trypanosoma cruzi, is a vector-borne parasitic disease, and dogs are a major domestic host of the parasite. We performed the first randomized field trial of an immunotherapeutic vaccine among client-owned dogs with natural infections and investigated immune correlates of efficacy. Thirty one dogs with T. cruzi infection received three doses of Tc24-C4 and TSA1-C4 recombinant proteins with MPLA (N = 16) or saline control (N = 15) and were followed for six months. Therapeutic vaccination decreased parasite burden, prevented/stopped cardiac alterations measured by electrocardiographic (ECG) recordings and was safe. Vaccine treatment induced changes in T cell activation and T cell receptor (TCR) repertoire, and also inhibited the ongoing innate immune response to reduce inflammation, suggesting a complex interplay between innate and T cells. These results support the further development of a vaccine based on these antigens to prevent the progression of chronic cardiac disease from T. cruzi infection.