Bet v 1 contiguous overlapping peptides anchored to virosomes with TLR4 agonist enhance immunotherapy efficacy in mice.
Adjuvants, Immunologic
/ pharmacology
Animals
Antigens, Plant
/ administration & dosage
Asthma
/ immunology
Betula
/ immunology
Bronchoalveolar Lavage Fluid
/ cytology
Disease Models, Animal
Immunoglobulin E
/ drug effects
Immunoglobulin G
/ drug effects
Mice
Peptides
/ administration & dosage
Rhinitis, Allergic, Seasonal
/ immunology
Sublingual Immunotherapy
/ methods
T-Lymphocytes
/ drug effects
Th1-Th2 Balance
/ drug effects
Toll-Like Receptor 2
/ agonists
Toll-Like Receptor 4
/ agonists
Toll-Like Receptor 7
/ agonists
Virosomes
Bet v 1 contiguous overlapping peptides
allergen immunotherapy
virosomes
Journal
Clinical and experimental allergy : journal of the British Society for Allergy and Clinical Immunology
ISSN: 1365-2222
Titre abrégé: Clin Exp Allergy
Pays: England
ID NLM: 8906443
Informations de publication
Date de publication:
02 2021
02 2021
Historique:
received:
17
07
2020
revised:
30
11
2020
accepted:
15
12
2020
pubmed:
29
12
2020
medline:
15
1
2022
entrez:
28
12
2020
Statut:
ppublish
Résumé
Whereas sublingual allergen immunotherapy (AIT) is routinely performed without any adjuvant or delivery system, there is a strong scientific rationale to better target the allergen(s) to oral dendritic cells known to support regulatory immune responses by using appropriate presentation platforms. To identify a safe presentation platform able to enhance allergen-specific tolerance induction. Virosomes with membrane-integrated contiguous overlapping peptides (COPs) of Bet v 1 and TLR4 or TLR2/TLR7 agonists were assessed for induction of Bet v 1-specific IgG1, IgG2a and IgE antibodies, hypersensitivity reactions and body temperature drop following subcutaneous injection in naive CD-1 mice. The most promising candidate, Bet v 1 COPs anchored to virosomes with membrane-incorporated TLR4 agonist (Vir.A-Bet v 1 COPs), was further evaluated by the sublingual route in a therapeutic setting in BALB/c mice with birch pollen-induced allergic asthma. Airway hyperresponsiveness, pro-inflammatory cells in bronchoalveolar lavages and polarization of Th cells in the lungs and spleen were then assessed. Both types of adjuvanted virosomes coupled to Bet v 1 COPs triggered a boosted Th1 immunity. Given a more favourable safety profile, Vir.A-Bet v 1 COPs were further evaluated and shown to able to fully reverse asthma symptoms and lung inflammation in a sublingual therapeutic model of birch pollen allergy. We report herein for the first time on the capacity of a novel and safe presentation platform, that is virosomes with membrane-integrated TLR4 agonist, to improve dramatically sublingual AIT efficacy in a murine model due to its intrinsic dual properties of targeting and stimulating to further promote anti-allergic immune responses. As such, our study paves the ground for further clinical development of this allergen presentation platform for patients suffering from respiratory allergies.
Sections du résumé
BACKGROUND
Whereas sublingual allergen immunotherapy (AIT) is routinely performed without any adjuvant or delivery system, there is a strong scientific rationale to better target the allergen(s) to oral dendritic cells known to support regulatory immune responses by using appropriate presentation platforms.
OBJECTIVE
To identify a safe presentation platform able to enhance allergen-specific tolerance induction.
METHODS
Virosomes with membrane-integrated contiguous overlapping peptides (COPs) of Bet v 1 and TLR4 or TLR2/TLR7 agonists were assessed for induction of Bet v 1-specific IgG1, IgG2a and IgE antibodies, hypersensitivity reactions and body temperature drop following subcutaneous injection in naive CD-1 mice. The most promising candidate, Bet v 1 COPs anchored to virosomes with membrane-incorporated TLR4 agonist (Vir.A-Bet v 1 COPs), was further evaluated by the sublingual route in a therapeutic setting in BALB/c mice with birch pollen-induced allergic asthma. Airway hyperresponsiveness, pro-inflammatory cells in bronchoalveolar lavages and polarization of Th cells in the lungs and spleen were then assessed.
RESULTS
Both types of adjuvanted virosomes coupled to Bet v 1 COPs triggered a boosted Th1 immunity. Given a more favourable safety profile, Vir.A-Bet v 1 COPs were further evaluated and shown to able to fully reverse asthma symptoms and lung inflammation in a sublingual therapeutic model of birch pollen allergy.
CONCLUSIONS AND CLINICAL RELEVANCE
We report herein for the first time on the capacity of a novel and safe presentation platform, that is virosomes with membrane-integrated TLR4 agonist, to improve dramatically sublingual AIT efficacy in a murine model due to its intrinsic dual properties of targeting and stimulating to further promote anti-allergic immune responses. As such, our study paves the ground for further clinical development of this allergen presentation platform for patients suffering from respiratory allergies.
Substances chimiques
Adjuvants, Immunologic
0
Antigens, Plant
0
Immunoglobulin G
0
Peptides
0
Toll-Like Receptor 2
0
Toll-Like Receptor 4
0
Toll-Like Receptor 7
0
Virosomes
0
Bet v 1 allergen, Betula
126161-14-6
Immunoglobulin E
37341-29-0
Types de publication
Journal Article
Langues
eng
Sous-ensembles de citation
IM
Pagination
339-349Informations de copyright
© 2020 John Wiley & Sons Ltd.
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