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Open AccessArticle

Design of Polymeric Nanocapsules for Intranasal Vaccination against Mycobacterium Tuberculosis: Influence of the Polymeric Shell and Antigen Positioning

1
Inmunología, Centro de Investigaciones Biomédicas, CINBIO, Universidade de Vigo, Campus Universitario Lagoas Marcosende, 36310 Vigo, Spain
2
Instituto de Investigación Sanitaria Galicia Sur (IIS-GS), SERGAS-UVIGO, Estrada de Clara Campoamor, 341, 36312 Vigo, PO, Spain
3
Department of Pharmacology, Pharmacy and Pharmaceutical Technology, School of Pharmacy, Campus Vida, Center for Research in Molecular Medicine and Chronic Diseases (CIMUS), IDIS Research Institute, Universidade de Santiago de Compostela, 15782 Santiago de Compostela, Spain
4
Institute for Infection and Immunity, St George’s Medical School, London SW17 0RE, UK
5
Lionex GmbH, 38126 Braunschweig, Germany
*
Authors to whom correspondence should be addressed.
Pharmaceutics 2020, 12(6), 489; https://doi.org/10.3390/pharmaceutics12060489
Received: 14 May 2020 / Revised: 26 May 2020 / Accepted: 26 May 2020 / Published: 28 May 2020
(This article belongs to the Special Issue Tuberculosis Vaccine Research and Development)
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. View Full-Text
Keywords: 6 kDa early secretory antigenic target (ESAT-6); 10 kDa culture filtrate protein (CFP-10); vaccination; Imiquimod; Toll-like receptor-7 (TLR-7); antibodies; cytokines; complement system; reactive oxygen species (ROS) 6 kDa early secretory antigenic target (ESAT-6); 10 kDa culture filtrate protein (CFP-10); vaccination; Imiquimod; Toll-like receptor-7 (TLR-7); antibodies; cytokines; complement system; reactive oxygen species (ROS)
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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.

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