Back to Search
Start Over
Bet v 1 contiguous overlapping peptides anchored to virosomes with TLR4 agonist enhance immunotherapy efficacy in mice.
- Source :
-
Clinical and experimental allergy : journal of the British Society for Allergy and Clinical Immunology [Clin Exp Allergy] 2021 Feb; Vol. 51 (2), pp. 339-349. Date of Electronic Publication: 2021 Jan 06. - Publication Year :
- 2021
-
Abstract
- 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.<br />Objective: To identify a safe presentation platform able to enhance allergen-specific tolerance induction.<br />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.<br />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.<br />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.<br /> (© 2020 John Wiley & Sons Ltd.)
- Subjects :
- Animals
Antigens, Plant administration & dosage
Betula immunology
Bronchoalveolar Lavage Fluid cytology
Disease Models, Animal
Immunoglobulin E immunology
Immunoglobulin G immunology
Mice
Peptides administration & dosage
Peptides pharmacology
T-Lymphocytes immunology
Th1-Th2 Balance drug effects
Toll-Like Receptor 2 agonists
Toll-Like Receptor 4 agonists
Toll-Like Receptor 7 agonists
Virosomes
Adjuvants, Immunologic pharmacology
Antigens, Plant pharmacology
Asthma immunology
Immunoglobulin E drug effects
Immunoglobulin G drug effects
Rhinitis, Allergic, Seasonal immunology
Sublingual Immunotherapy methods
T-Lymphocytes drug effects
Subjects
Details
- Language :
- English
- ISSN :
- 1365-2222
- Volume :
- 51
- Issue :
- 2
- Database :
- MEDLINE
- Journal :
- Clinical and experimental allergy : journal of the British Society for Allergy and Clinical Immunology
- Publication Type :
- Academic Journal
- Accession number :
- 33368719
- Full Text :
- https://doi.org/10.1111/cea.13814