Vaccine against Trypanosoma cruzi infection using the Parasite Antigen TcTASV Displayed at Baculovirus Capsid

Chagas' is a neglected disease caused by the eukaryotic kinetoplastid parasite Trypanosoma cruzi. Currently there are about 8 million infected people worldwide, most of them at the chronic phase of the disease, which involves cardiac, digestive or neurologic manifestations. There is an urgent need for a vaccine because treatments are only effective at the initial phase of the infection, which is generally underdiagnosed. Selection and combination of antigens, adjuvants, and delivery platforms for vaccine formulations should be designed to trigger mixed humoral and cellular immune responses, considering that T. cruzi has a complex life cycle with both intracellular and bloodstream circulating parasite stages in the vertebrate host. Here we report the effectiveness of the vaccination with a T. cruzi-specific protein family (TcTASV), employing both recombinant proteins with aluminum hydroxide and recombinant baculovirus displaying a TcTASV antigen at the capsid. Vaccination stimulated immunological responses with production of lytic antibodies and antigen-specific CD4+ and CD8+ IFNɣ secreting lymphocytes. More than 90% of vaccinated animals survived after lethal challenges with T. cruzi while all control mice died before 30 days post infection. Vaccination also induced a strong decrease of chronic tissue parasitism, and generated immunological memory that allowed vaccinated and infected animals to control both the reactivation of the infection after immunosuppression as well as a second challenge with T. cruzi. Interestingly, inoculation with wild type baculovirus trained the immune system to partially protect mice against T. cruzi. In brief, we demonstrated, for the first time, that the combination of the baculovirus platform and the TcTASV family provides effective protection against Trypanosoma cruzi, being a promising vaccine for Chagas’ disease.