DEVELOPMENT OF A NEW VACCINE ADJUVANT, STUDY OF ITS MECHANISM OF ACTION AND USES THEREOF

CARABAJAL MV; CORIA LM; BRUNO LA; DARRIBA ML; MARTÍNEZ FL; IBÁÑEZ AE; PASQUEVICH KA; CASSATARO J

Buenos Aires

Jornada; XVIII Jornadas Anuales Multidisciplinarias. Sociedad Argentina de Biología; 2016

Sociedad Argentina de Biología

In our laboratory we are working with a Brucella abortus protein called U-Omp19. We demonstrated that U-Omp19 is a broad spectrum protease inhibitor. U-Omp19 inhibited the aspartic protease pepsin, serin proteases (pancreatic elastase, trypsin and α-chymotrypsin), and cystein proteases (cathepsin L, B and S). Stability studies showed that U-Omp19 retained its full protease inhibitor activity when previously exposed to a broad pH (2-8) or temperature (25-100°C) range. U-Omp19 behaves as an important component of vaccine formulations against infectious diseases. When co-delivered orally with an antigen (Ag), U-Omp19: i) can bypass the harsh environment of the gastrointestinal tract by inhibiting stomach and intestine proteases and consequently increases the half-life of the co-delivered Ag at immune inductive sites: Peyer's Patches and mesenteric lymph nodes while ii) it induces the recruitment and activation of antigen presenting cells (APCs) and increases the amount of intracellular Ag inside APCs. Besides, U-Omp19 reduces the amount of digested Ag within APCs at inductive sites increasing Ag cross presentation. Therefore, mucosal as well as systemic Ag-specific immune responses, antibodies, Th1, Th17 and CD8+ T cells are enhanced when U-Omp19 is co-delivered with the Ag orally. Finally, this bacterial protease inhibitor in oral vaccine formulations confers mucosal protection against LT or CT-induced diarrhea, and reduces bacterial or parasite loads after oral challenge with virulent Salmonella, Enterohemorrhagic Escherichia coli O157:H7 or Toxoplasma gondii.