Methylglycol chitosan and a synthetic TLR4 agonist enhance immune responses to influenza vaccine administered sublingually |
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| Affiliation: | 1. GlaxoSmithKline Vaccines, 553 Old Corvallis Road, Hamilton, MT 59840, USA;2. 1910 Country Drive Apartment 202, Grayslake, IL 60030, USA;3. 3067 Bugli Lane, Stevensville, MT 59870, USA;4. GlaxoSmithKline Vaccines, 525 Cartier Ouest, Laval, QC, Canada H7V 3S8;5. Neomed Institute, 7171 Frederick Banting, Montreal, QC, Canada H4S 1Z9;1. Research and Educational Centre ENGEC, Ural Federal University, Mira 19, 620002, Ekaterinburg, Russia;2. Department of Oil and Gas Processing, Tyumen Industrial University, Volodarsky 38, 625000, Tyumen, Russia;1. Pharmacokinetic, Nanotechnology and Gene Therapy Group (PharmaNanoGene), Faculty of Pharmacy, Centro de Investigación Lascaray Ikergunea, University of the Basque Country UPV/EHU, Vitoria-Gasteiz, Spain;2. Université Catholique de Louvain, Louvain Drug Research Institute, Pharmaceutics and Drug Delivery, Brussels 1200, Belgium;1. Nanomedical Systems Laboratory, SKKU Advanced Institute of Nanotechnology (SAINT), School of Chemical Engineering, Sungkyunkwan University, Suwon 440-746, Republic of Korea;2. Laboratory of Immunology and Infectious Diseases, Graduate School of Medical Science and Engineering, KAIST, 291 Daehak-ro, Daejeon 305-701, Republic of Korea;1. Department of Medical and Surgical Sciences, University of Foggia, Viale L. Pinto 1, 71122 Foggia, Italy;2. Department of Pharmacy-Drug Sciences, University of Bari “Aldo Moro”, Via Orabona, 4, 70125 Bari, Italy;3. Medical Genetics Laboratory, Fondazione IRCCS Ca'' Granda Ospedale Maggiore Policlinico, Via Commenda 12, 20122 Milan, Italy;4. Biological Chemical and Pharmaceutical Sciences and Technologies (STEBICEF), Laboratory of Biocompatible Polymers, University of Palermo, Via Archirafi 32, 90123 Palermo, Italy;5. Dipartimento di Scienze del Farmaco, Università degli Studi di Catania, Viale A. Doria, 6, 95125 Catania, Italy |
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| Abstract: | Influenza is a vaccine-preventable contagious respiratory illness caused by influenza (flu) viruses which can lead to hospitalization and sometimes even death. Current flu vaccines delivered intramuscularly (IM) or intradermally (ID) are less effective at eliciting protective mucosal immune responses and vaccines delivered intranasally (IN) possess potential safety concerns. Sublingual (SL) vaccination is a promising alternative route for vaccine delivery which has been indicated as safe and effective at inducing protective immune responses in both systemic and mucosal compartments. We evaluated the efficacy of methylglycol chitosan (MGC) and a synthetic toll-like receptor 4 agonist (CRX-601), alone or in combination, for improving systemic and mucosal immune responses to a monovalent detergent-split flu virus vaccine delivered SL. SL vaccination of mice with split-flu vaccine formulated with either MGC or CRX-601 resulted in specific serum IgG and mucosal IgA titers that were significantly greater than titers from non-adjuvanted vaccination and equivalent to or greater than titers in mice vaccinated IM. Our results demonstrate that SL vaccination utilizing MGC or CRX-601 as adjuvants is a viable alternative route of vaccination for flu which can elicit systemic immune responses equivalent to or greater than IM vaccination with the added benefit of stimulating a robust specific mucosal immune response. |
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| Keywords: | Sublingual TLR-4 Chitosan Influenza Mucosal vaccination CRX-601 |
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