VACCINE AGAINST TRYPANOSOMA CRUZI INFECTION USING THE PARASITE ANTIGEN TcTASV DISPLAYED AT BACULOVIRUS CAPSID

MASIP Y; CAEIRO, L; COSENZA, M; POSTAN M.; MOLINA, G; TABOGA, OA; MOLINARI, MP; TEKIEL V

San Luis

Congreso; SAI Reunion Anual 2023; 2023

SAI

VACCINE AGAINST TRYPANOSOMA CRUZI INFECTION USING THE PARASITE ANTIGEN TcTASV DISPLAYED AT BACULOVIRUS CAPSIDYamil Ezequiel Masip1,2*, Lucas Caeiro1,2, Maximiliano Cosenza1,2, Miriam Postan3, Guido Molina4, Oscar Taboga4, M. Paula Molinari4, Valeria Tekiel1,21Instituto de Investigaciones Biotecnológicas, – Consejo Nacional de Investigaciones Científicas y Técnicas (CONICET), Buenos Aires, Argentina. 2 Escuela de Bio y Nanotecnologías (EByN), Universidad Nacional de San Martín (UNSAM), Buenos Aires, Argentina 3 Consejo Nacional de Investigaciones Científicas y Técnicas (CONICET), Buenos Aires, Argentina.4 Instituto de Agrobiotecnología y Biología Molecular (IABIMO), Instituto Nacional de Tecnología Agropecuaria (INTA), Consejo Nacional de Investigaciones Científicas y Técnicas (CONICET), Buenos Aires, Argentina.* Corresponding author at ymasip@iib.unsam.edu.arChagas´ 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 (amastigotes) and bloodstream circulating (trypomastigotes) parasite stages in the vertebrate host. TcTASV is a T. cruzi multigene family highly conserved among lineages and without orthologs in other organisms, including trypanosomatids. TcTASV has approximately 40 members that can be classified in subfamilies according to close sequence similarity. TcTASV-A and TcTASV-C are the most abundant subfamilies, present the highest levels of expression and both are in contact with the host immune system in vivo. TcTASV-A subfamily is expressed both in trypomastigotes and amastigotes, with an intracellular location. TcTASV-C subfamily is solely expressed in trypomastigotes, located at T. cruzi surface, and secreted both freely and contained in extracellular vesicles. Here we report the effectiveness of the vaccination TcTASV protein family, which consisted in a prime with TcTASV-C recombinant protein with aluminum hydroxide and a boost with recombinant baculovirus displaying a TcTASV-A antigen at the capsid. Vaccination stimulated immunological responses with production of lytic antibodies and antigen-specific CD4+ and CD8+ IFNɣ-secreting lymphocytes. After several assays with similar results, an average of 92% of vaccinated animals survived to lethal challenges with T. cruzi (RA strain, high virulence) while all control mice died before 30 days post infection. Vaccination also induced a strong decrease of tissue parasitism at the chronic phase, 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. Similar results were obtained in another mice strain, and additional trials are ongoing to evaluate the protective capacity against another parasite strain. Interestingly, inoculation with wild type baculovirus partially protected 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.SELECCIONADO PARA PARTICIPAR por PREMIO L. SATZ