Diego González, LaraCrecente Campo, JoséPaul, Matthew JohnSingh, MahavirReljic, RajkoAlonso Fernández, María JoséGonzález Fernández, ÁfricaSimón Vázquez, Rosana2020-11-262020-11-262020Diego-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, 489http://hdl.handle.net/10347/23814Tuberculosis (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 nanocarriereng© 2020 by the authors. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (http://creativecommons.org/licenses/by/4.0/)Atribución 4.0 Internacionalhttp://creativecommons.org/licenses/by/4.0/6 kDa early secretory antigenic target (ESAT-6)10 kDa culture filtrate protein (CFP-10)VaccinationImiquimodToll-like receptor-7 (TLR-7)AntibodiesCytokinesComplement systemReactive oxygen species (ROS)journal article10.3390/pharmaceutics120604891999-4923open access