Mucosal Adjuvants Delivered by a Mucoadhesive Patch for Sublingual Administration of Subunit Vaccines

Among mucosal administration routes for vaccines, the sublingual route has been proven capable of inducing a potent systemic and mucosal immune response. However, the absence of a simple and compliant delivery system and the lack of robust mucosal adjuvants impede the development of sublingual vacci...

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Main Authors: Claire Monge, Camille Ayad, Anne-Lise Paris, Renaud Rovera, Evelyne Colomb, Bernard Verrier
Format: Article
Language:English
Published: MDPI AG 2022-11-01
Series:International Journal of Molecular Sciences
Subjects:
Online Access:https://www.mdpi.com/1422-0067/23/21/13440
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author Claire Monge
Camille Ayad
Anne-Lise Paris
Renaud Rovera
Evelyne Colomb
Bernard Verrier
author_facet Claire Monge
Camille Ayad
Anne-Lise Paris
Renaud Rovera
Evelyne Colomb
Bernard Verrier
author_sort Claire Monge
collection DOAJ
description Among mucosal administration routes for vaccines, the sublingual route has been proven capable of inducing a potent systemic and mucosal immune response. However, the absence of a simple and compliant delivery system and the lack of robust mucosal adjuvants impede the development of sublingual vaccines. Here, we describe a mucoadhesive patch made of a layer-by-layer assembly of polysaccharides, chitosan, and hyaluronic acid. The mucoadhesive patch was covered by adjuvanted nanoparticles carrying viral proteins. We showed that the nanoparticles effectively cross the outer layers of the sublingual mucosa to reach the epithelium. Furthermore, the encapsulated adjuvants, 3M-052 and mifamurtide, targeting toll-like receptor (TLR) 7/8 and nucleotide-binding oligomerization domain-2 (NOD2), respectively, remain fully active after encapsulation into nanoparticles and exhibit a cytokine/chemokine signature similar to the mucosal gold-standard adjuvant, the cholera toxin. However, the particulate adjuvants induced more moderate levels of proinflammatory interleukin (IL)-6 and keratinocyte chemoattractant (KC), suggesting a controlled activation of the innate immune response.
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spelling doaj.art-f94e7f2050424ccdae884225ea4869042023-11-24T05:07:57ZengMDPI AGInternational Journal of Molecular Sciences1661-65961422-00672022-11-0123211344010.3390/ijms232113440Mucosal Adjuvants Delivered by a Mucoadhesive Patch for Sublingual Administration of Subunit VaccinesClaire Monge0Camille Ayad1Anne-Lise Paris2Renaud Rovera3Evelyne Colomb4Bernard Verrier5UMR 5305: Laboratoire de Biologie Tissulaire et d’Ingénierie Thérapeutique, Institut de Biologie et Chimie des Protéines, CNRS/Université Claude Bernard Lyon 1, 7 Passage du Vercors, 69007 Lyon, FranceUMR 5305: Laboratoire de Biologie Tissulaire et d’Ingénierie Thérapeutique, Institut de Biologie et Chimie des Protéines, CNRS/Université Claude Bernard Lyon 1, 7 Passage du Vercors, 69007 Lyon, FranceUMR 5305: Laboratoire de Biologie Tissulaire et d’Ingénierie Thérapeutique, Institut de Biologie et Chimie des Protéines, CNRS/Université Claude Bernard Lyon 1, 7 Passage du Vercors, 69007 Lyon, FranceUMR 5305: Laboratoire de Biologie Tissulaire et d’Ingénierie Thérapeutique, Institut de Biologie et Chimie des Protéines, CNRS/Université Claude Bernard Lyon 1, 7 Passage du Vercors, 69007 Lyon, FranceUMR 5305: Laboratoire de Biologie Tissulaire et d’Ingénierie Thérapeutique, Institut de Biologie et Chimie des Protéines, CNRS/Université Claude Bernard Lyon 1, 7 Passage du Vercors, 69007 Lyon, FranceUMR 5305: Laboratoire de Biologie Tissulaire et d’Ingénierie Thérapeutique, Institut de Biologie et Chimie des Protéines, CNRS/Université Claude Bernard Lyon 1, 7 Passage du Vercors, 69007 Lyon, FranceAmong mucosal administration routes for vaccines, the sublingual route has been proven capable of inducing a potent systemic and mucosal immune response. However, the absence of a simple and compliant delivery system and the lack of robust mucosal adjuvants impede the development of sublingual vaccines. Here, we describe a mucoadhesive patch made of a layer-by-layer assembly of polysaccharides, chitosan, and hyaluronic acid. The mucoadhesive patch was covered by adjuvanted nanoparticles carrying viral proteins. We showed that the nanoparticles effectively cross the outer layers of the sublingual mucosa to reach the epithelium. Furthermore, the encapsulated adjuvants, 3M-052 and mifamurtide, targeting toll-like receptor (TLR) 7/8 and nucleotide-binding oligomerization domain-2 (NOD2), respectively, remain fully active after encapsulation into nanoparticles and exhibit a cytokine/chemokine signature similar to the mucosal gold-standard adjuvant, the cholera toxin. However, the particulate adjuvants induced more moderate levels of proinflammatory interleukin (IL)-6 and keratinocyte chemoattractant (KC), suggesting a controlled activation of the innate immune response.https://www.mdpi.com/1422-0067/23/21/13440sublingualadjuvantnanoparticlemucoadhesivecytokine profilinglayer by layer
spellingShingle Claire Monge
Camille Ayad
Anne-Lise Paris
Renaud Rovera
Evelyne Colomb
Bernard Verrier
Mucosal Adjuvants Delivered by a Mucoadhesive Patch for Sublingual Administration of Subunit Vaccines
International Journal of Molecular Sciences
sublingual
adjuvant
nanoparticle
mucoadhesive
cytokine profiling
layer by layer
title Mucosal Adjuvants Delivered by a Mucoadhesive Patch for Sublingual Administration of Subunit Vaccines
title_full Mucosal Adjuvants Delivered by a Mucoadhesive Patch for Sublingual Administration of Subunit Vaccines
title_fullStr Mucosal Adjuvants Delivered by a Mucoadhesive Patch for Sublingual Administration of Subunit Vaccines
title_full_unstemmed Mucosal Adjuvants Delivered by a Mucoadhesive Patch for Sublingual Administration of Subunit Vaccines
title_short Mucosal Adjuvants Delivered by a Mucoadhesive Patch for Sublingual Administration of Subunit Vaccines
title_sort mucosal adjuvants delivered by a mucoadhesive patch for sublingual administration of subunit vaccines
topic sublingual
adjuvant
nanoparticle
mucoadhesive
cytokine profiling
layer by layer
url https://www.mdpi.com/1422-0067/23/21/13440
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