Catarina Remedios

Currently, injection-based vaccination is the most common method for influenza immunization. However, parenteral vaccination fails to induce mucosal immune responses, representing an important first line of defense. Under the framework of the UniVacFlu project, this study was undertaken to assess the potential of the universal influenza vaccine candidate CTA1-3M2e-DD as an oral vaccine, along with that of cationic polysaccharide nanoparticles (NPL) as an oral vaccine delivery system. We found that, while CTA1-3M2e-DD revealed a poor ability to cross the intestinal epithelium and target lamina propria antigen-presenting cells, NPL readily overcome the intestinal barrier and are phagocytosed by both CX3CR1+ macrophages and CD103+ dendritic cells. Two different routes of NPL uptake were identified: one depends on Goblet cell-associated passages that allow the transfer of high amounts of NPL from the lumen into the intestinal lamina propria; the second relies on the direct acquisition of NPL by CX3CR1+ cells in Peyer’s patches through extension of trans-epithelial dendrites. Moreover, using our model of oral immunization that protects NPL from the stomach pH, the vaccine vector was able to deliver the loaded antigen in the intestinal lamina propria and enhanced antigen presentation to CD4+ T lymphocytes in different organs. Despite increasing antigen presentation, NPL did not induce tolerance towards the formulated antigen and a Th1 immune response was found at the level of the Peyer’s patches. We also identified the contribution of the starvation period in the immune response induced by the NPL formulation in our model of oral immunization.