Polymeric nanoparticles targeted to M cells for an oral immunization
(2008)
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- Abstract
- Vaccination saves millions of lives every year and is considered to be the most cost-effective method of preventing infectious diseases. Despite the success of traditional injected vaccines, the vast majority of infections occurs at mucosal surfaces. Contrary to parenteral vaccines, mucosal vaccines have the ability to confer a protective local immunity at mucosal sites in addition of a systemic immune response. Last decades, for safety reasons, there has been a shift from traditional mucosal vaccines that are mainly composed of live-attenuated or killed pathogens, towards a new generation of vaccines composed of sub-unit immunogens. To facilitate the effective immunization, those compounds are associated with adjuvants, which stimulate the immune system. For oral immunization they must also be protected against degradation in the harsh gastro-intestinal environment and their uptake by intestinal specialized antigen-sampling cells, called M cells, must be enhanced. One of the main approaches proposed to enhance the stability and the availibility of orally administered antigens, relies on their association with delivery systems, such as polymeric nanoparticles. Hence, the main objective of this thesis was to develop a polymer-based formulation encapsulating a model antigen and to improve their transcytosis by targeting M cells, in view of an oral immunization. The main issues raised by this research concern: (i) the development of a reproducible and reliable in vitro model of human FAE serving as a tool to deeper elucidate M cell transport mechanisms; (ii) the search of new surface markers, as receptors/alternative targets in human FAE; (iii) the optimization of surface properties of nanoparticles for their optimal targeting and uptake by M cells. This in vitro work was complemented by several immunization studies carried out in vivo. Results obtained in this thesis indicated that transmucosal uptake of vaccine particles could be improved via their targeting to the M cell apical surface. In addition, these parameters seem to influence the profile and the intensity of the immune response obtained after oral vaccination.
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Citations
Fievez, V. (2008). Polymeric nanoparticles targeted to M cells for an oral immunization. https://hdl.handle.net/2078.5/98552