1. Academic Validation
  2. Mucoadhesive film for oral delivery of vaccines for protection of the respiratory tract

Mucoadhesive film for oral delivery of vaccines for protection of the respiratory tract

  • J Control Release. 2024 Jul:371:179-192. doi: 10.1016/j.jconrel.2024.05.041.
Hana Esih 1 Klemen Mezgec 1 Martina Billmeier 2 Špela Malenšek 1 Mojca Benčina 3 Blaž Grilc 4 Sara Vidmar 1 Mirjana Gašperlin 4 Marjan Bele 5 Mihaela Zidarn 6 Tatjana Lejko Zupanc 7 Tina Morgan 6 Ingo Jordan 8 Volker Sandig 8 Silke Schrödel 9 Christian Thirion 9 Ulrike Protzer 10 Ralf Wagner 11 Duško Lainšček 12 Roman Jerala 13
Affiliations

Affiliations

  • 1 Department of Synthetic Biology and Immunology, National Institute of Chemistry, 1000 Ljubljana, Slovenia; Graduate School of Biomedicine, University of Ljubljana, 1000 Ljubljana, Slovenia.
  • 2 Institute of Medical Microbiology & Hygiene, Molecular Microbiology (Virology), University of Regensburg, Regensburg, Germany.
  • 3 Department of Synthetic Biology and Immunology, National Institute of Chemistry, 1000 Ljubljana, Slovenia; Centre for Technologies of Gene and Cell Therapy, 1000 Ljubljana, Slovenia.
  • 4 University of Ljubljana, Faculty of Pharmacy, Department of Pharmaceutical Technology, Ljubljana 1000, Slovenia.
  • 5 Department of Materials Chemistry, National Institute of Chemistry, Ljubljana 1000, Slovenia.
  • 6 University Clinic of Pulmonary and Allergic Diseases Golnik, Golnik, Slovenia.
  • 7 University Medical Center Ljubljana, 1000 Ljubljana, Slovenia.
  • 8 Applied Science & Technologies, ProBioGen AG, Berlin, Germany.
  • 9 SIRION Biotech GmbH, Am Klopferspitz 19, 82152 Martinsried, Germany.
  • 10 Institute of Virology, School of Medicine, Technical University of Munich, Helmholtz Zentrum München, Munich, Germany.
  • 11 Institute of Medical Microbiology & Hygiene, Molecular Microbiology (Virology), University of Regensburg, Regensburg, Germany; Institute of Clinical Microbiology & Hygiene, University Hospital, Regensburg, Germany.
  • 12 Department of Synthetic Biology and Immunology, National Institute of Chemistry, 1000 Ljubljana, Slovenia; Centre for Technologies of Gene and Cell Therapy, 1000 Ljubljana, Slovenia. Electronic address: dusko.lainscek@ki.si.
  • 13 Department of Synthetic Biology and Immunology, National Institute of Chemistry, 1000 Ljubljana, Slovenia; Centre for Technologies of Gene and Cell Therapy, 1000 Ljubljana, Slovenia. Electronic address: roman.jerala@ki.si.
Abstract

The delivery of vaccines plays a pivotal role in influencing the strength and longevity of the immune response and controlling reactogenicity. Mucosal immunization, as compared to parenteral vaccination, could offer greater protection against respiratory infections while being less invasive. While oral vaccination has been presumed less effective and believed to target mainly the gastrointestinal tract, trans-buccal delivery using mucoadhesive films (MAF) may allow targeted delivery to the mucosa. Here we present an effective strategy for mucosal delivery of several vaccine platforms incorporated in MAF, including DNA plasmids, viral vectors, and lipid nanoparticles incorporating mRNA (mRNA/LNP). The mRNA/LNP vaccine formulation targeting SARS-CoV-2 as a proof of concept remained stable within MAF consisting of slowly releasing water-soluble Polymers and an impermeable backing layer, facilitating enhanced penetration into the oral mucosa. This formulation elicited antibody and cellular responses comparable to the intramuscular injection, but also induced the production of mucosal IgAs, highlighting its efficacy, particularly for use as a booster vaccine and the potential advantage for protection against respiratory infections. The MAF vaccine preparation demonstrates significant advantages, such as efficient delivery, stability, and simple noninvasive administration with the potential to alleviate vaccine hesitancy.

Keywords

Mucoadhesive film; Mucosal immunity; Respiratory infection; Vaccine delivery.

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