SCOUTING BACTERIAL OUTER MEMBRANE VESICLES AS BIOACTIVE ANTIGEN-CARRIERS IN THE DEVELOPMENT OF A NOVEL VACCINE STRATEGY FOR CHAGAS DISEASE

ZABALA B; JOSEPH SPANGLER; ANDREA C. MESÍAS; SCOTT A. WALPER; CECILIA PÉREZ BRANDÁN; VÁZQUEZ ME; PARODI C; LEONARDO ACUÑA

Buenos Aires

Workshop; EVs in immunology; 2020

International Society for Extracellular Vesicles

Outer membrane vesicles (OMVs) are nanoparticles released from bacteria, rich in immunomodulatory proteins and lipopolysaccharides. Some 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 infectious diseases. With this in mind, we aimed 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, named 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 recombinant OMVs (rOMVs) were preliminarily evaluated in a murine prime-boost-challenge scheme for Chagas disease. For this purpose, mice were injected intradermally with two doses of rOMVs supplemented with ISPA adjuvant. During the vaccination stage, we determined IgGs subtypes levels and relevant cytokines in spleen cell culture-supernatants from 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 immunogen carrier. In summary, the results so far obtained indicate that genetically designed OMVs could be a possible platform for the development of novel strategies for trypanosomatids immunization.