NANOPARTICLES FOR MUCOSAL VACCINE DELIVERY
Creators: name: FORTUNA DOS REMEDIOS, CATARINA
Publisher: name: Universit� degli Studi di Milano
Year: 2018

description: Influenza is a contagious respiratory disease often disregarded due to the mild symptoms associated with it. The economic burden that flu cases impose on health care systems is substantial, not only due to influenza pandemics, but also to required hospitalizations and the need for yearly revisions of seasonal influenza vaccines. The need for a universal influenza vaccine was already recognized by the Global Vaccine Action Plan. Currently, injection-based vaccination is the most common method for influenza immunization. However, evidence has shown that mucosal immune responses, representing an important first line of defense at these sites, since most pathogens enter the body through mucosal tissues, are most efficiently induced by administration of vaccines onto mucosal surfaces than injected vaccines. From the different mucosal tissues, the gastrointestinal tract is an attractive route to be explored for vaccination; nonetheless, oral influenza vaccines are not available yet. The intestinal homeostasis is tightly controlled by several components of the intestinal barrier, such as the mucus layer, epithelial cells with different functions and an underlying immune system that surveys the gut. Between microorganisms that normally inhabit our gut, food antigens constantly present in our diet and potential pathogens, the intestinal barrier has the difficult task of integrating external and internal signals received by different cells in order to establish the correct response, immunity or tolerance, according to the antigen. Hence, oral vaccines will encounter these same intestinal barrier components and face the same obstacles as any other oral antigen or gut microorganism. The UniVacFlu consortium is currently working to develop a new mucosal universal vaccine against influenza, exploring different immunogens, immunization routes and delivery systems. This study was undertaken to understand the potential of the influenza vaccine candidate CTA1-3M2e-DD and polysaccharidic lipidated nanoparticles (NPL) when immunization occurs through the oral route. We found that, while CTA1-3M2e-DD revealed a poor ability to cross the intestinal epithelium and target intestinal antigen-presenting cells, NPL were found to readily overcome the intestinal barrier and were found associated with 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 to the intestinal lamina propria; the second relies on the direct acquisition of NPL by CX3CR1+ macrophages in Peyer?s patches by extension of trans-epithelial dendrites. Moreover, NPL as an oral 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 the availability of antigen, 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. The full potential of NPL as a vaccine vector is currently being further investigated to understand its immunomodulatory properties.