Engineered bacterial outer membrane vesicles as a technological platform for the development of a Chagas disease vaccine

SPANGLER JR; SANCHEZ VALDEZ F; MESIAS AC; PARODI, C; PEREZ BRANDAN C; ACUÑA LA; WALPER SA

Caxambu, Minas Gerais

Congreso; XXXIV Meeting of the Brazilian Society of Protozoology/XLIV Annual Meeting on Basic Research in Chagas disease; 2018

Sociedade Brasileira de Protozoologia

Outer membrane vesicles (OMVs) are nanoparticles released from bacteria rich in immunomodulatory proteins and lipopolysaccharides. Three of the most promising characteristics of OMVs are their high adjuvant capacity, their safety, and the possibility of generating genetically engineered vesicles carrying foreign polypeptides. Therefore, the utilization of OMVs as vaccines offers promising potential against a wide range of diseases. With this in mind we proposed to evaluate the potential role of engineered OMVs carrying different Trypanosoma cruzi antigens as an experimental immunogen against Chagas disease. For this, we selected two well known antigens which have been extensively evaluated in vaccination models against T. cruzi, Tc24 and Tc52. The rational of selecting these antigens is that as a first step we propose to elucidate the advantage of using OMVs as carriers of parasite antigens and evaluate their adjuvant properties. As the first time reported, we were able to obtain recombinant OMVs with the selected T. cruzi antigens expressed not only on the outside of the vesicles but packaged within the lumen as well. These rOMVs were preliminarily evaluated in a murine prime-boot-challenge scheme for Chagas disease. For this purpose mice were injected intradermally with three separately doses of rOMVs. During the vaccination stage, a slight increase in IFN- production was detected in immunized animals. Thirty days after the last dose mice were challenged with a lethal dose of virulent parasites. Although not significant, a mild decrease in parasite load in vaccinated animals versus control groups could be detected. Several factors still need to be tested in order to optimize the use of rOMVs as a possible vaccine. In summary, the results so far obtained indicate that genetically designed OMVs could be a possible path for the development of novel strategies for trypanosomatids immunization. Funding: Fundación Bunge y Born y Florencio Fiorini.