RT Journal Article T1 Design of Polymeric Nanocapsules for Intranasal Vaccination against Mycobacterium Tuberculosis: Influence of the Polymeric Shell and Antigen Positioning A1 Diego González, Lara A1 Crecente Campo, José A1 Paul, Matthew John A1 Singh, Mahavir A1 Reljic, Rajko A1 Alonso Fernández, María José A1 González Fernández, África A1 Simón Vázquez, Rosana K1 6 kDa early secretory antigenic target (ESAT-6) K1 10 kDa culture filtrate protein (CFP-10) K1 Vaccination K1 Imiquimod K1 Toll-like receptor-7 (TLR-7) K1 Antibodies K1 Cytokines K1 Complement system K1 Reactive oxygen species (ROS) AB Tuberculosis (TB) is the leading cause of death from a single infectious microorganism and Bacillus Calmette Guerin (BCG), the only authorized vaccine, does not confer protection against pulmonary TB. Based on the hypothesis that mucosal protection could help to prevent the infection at the site of entrance, the objective of this work was to develop an intranasal vaccine against Mycobacterium tuberculosis (Mtb), the microorganism that causes TB. Our approach consisted of the use of polymeric nanocapsules (NCs) with an oily core and a polymer shell made of chitosan (CS) or inulin/polyarginine (INU/pArg). The immunostimulant Imiquimod, a Toll-like receptor-7 (TLR-7) agonist, was encapsulated in the oily core and a fusion protein, formed by two antigens of Mtb, was absorbed either onto the NC surface (CS:Ag and INU:pArg:Ag) or between two polymer layers (INU:Ag:pArg) in order to assess the influence of the antigen positioning on the immune response. Although CS NCs were more immunostimulant than the INU/pArg NCs in vitro, the in vivo experiments showed that INU:pArg:Ag NCs were the only prototype inducing an adequate immunoglobulin A (IgA) response. Moreover, a previous immunization with BCG increased the immune response for CS NCs but, conversely, decreased for INU/pArg NCs. Further optimization of the antigen and the vaccination regime could provide an efficacious vaccine, using the INU:pArg:Ag NC prototype as nanocarrier PB MDPI YR 2020 FD 2020 LK http://hdl.handle.net/10347/23814 UL http://hdl.handle.net/10347/23814 LA eng NO Diego-González, L.; Crecente-Campo, J.; Paul, M.J.; Singh, M.; Reljic, R.; Alonso, M.J.; González-Fernández, Á.; Simón-Vázquez, R. Design of Polymeric Nanocapsules for Intranasal Vaccination against Mycobacterium Tuberculosis: Influence of the Polymeric Shell and Antigen Positioning. Pharmaceutics 2020, 12, 489 NO This work was supported by the EU Horizon2020 Eliciting Mucosal Immunity in Tuberculosis (EMI-TB) project [Grant Number 643558], Xunta de Galicia: Grupo de Referencia Competitivo (under Grant ED431C 2016/041 and ED431C 2017/09), centro singular de investigación de Galicia (accreditation 2019-2022) and the EU (European Regional Development Fund-ERDF)—Ref. ED431G2019/06 DS Minerva RD 24 abr 2026