CONICET | Buscador de Institutos y Recursos Humanos

Oral vaccines are easy to administer and can be more cost-effective to develop. However, it is difficult to make an effective and safe oral vaccine because antigens can be destroyed by enzymes that are in the stomach and intestine. In oral vaccines, antigens must be protected, uptake enhanced and the immune tolerance properly controlled. In previous studies, we found that a Brucella spp. protein of 19kDa (U-Omp19) was able to induce the maturation of dendritic cells in vivo and demonstrated to be good at inducing an immune response. This protein is soluble and easy to express and purify at high scales. It has significant homology with protease inhibitors from other bacteria. Therefore, this is an unconventional bacterial molecular pattern never explored for use in vaccines. We propose to use this protein to stimulate the delivery of antigens in mucosal tissues. We have demonstrated that this protein can inhibit in vitro the activity of proteases present in the stomach and gut. Oral delivery of the antigen in the presence of the protein prevented the antigen´s degradation in vivo by 50% in the stomach and intestine of mice without inducing any adverse effects like diarrhea or dehydration. Interestingly, this protease inhibitor is pH and thermal stable it retained its full activity when exposed to wide pH and temperature ranges-. These are important attributes that will allow it to withstand the harsh environment of the gastrointestinal tract and its use of this protein in vaccines without refrigeration. We also saw evidence that oral co-delivery of the protein can induce a T helper 1 and 17 immune response. This protein, as an adjuvant, induced a significant reduction in bacterial burden at spleen and liver, demonstrating to be a useful adjuvant in an oral killed vaccine formulation against Salmonella. Altogether these results indicate that this protein possesses the capability not only to induce an immune response but also inhibit the destruction of the antigen. This would mean that half as much of the antigen would be need to induce the same protection which could lower vaccine costs dramatically. This protein would constitute an ideal mucosal adjuvant by increasing the half-life of the antigen while bypassing immune tolerance and stimulating an appropriate immune response at the mucosal surfaces. We believe that if we finally learn how to effectively deliver oral vaccines, this will transform radically not only the vaccine industry but global health in general.