Immunotherapeutic efficacy of liposome-encapsulated refined allergen vaccines against Dermatophagoides pteronyssinus allergy

Chaisri, Urai; Tungtrongchitr, Anchalee; Indrawattana, Nitaya; Meechan, Panisara; Phurttikul, Watchara; Tasaniyananda, Natt; Saelim, Nawannaporn; Chaicumpa, Wanpen; Sookrung, Nitat

doi:10.1371/journal.pone.0188627

Cited by 15 publications

(11 citation statements)

References 92 publications

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“…Animal experiments have revealed that removing Tregs from mice before sensitization aggravates airway inflammation and airway hyperresponsiveness (AHR) (31). Tregs inhibit effector T cells and regulate allergic diseases by secreting IL-10 and TGF-β, leading to reduced production of Th2 cytokines (IL-4, IL-5 and IL-13) (32). An approach to enhance the anti-allergic efficacy of therapeutic DNA vaccines was performed by fusion of a modulating cytokine such as GM-CSF, IFN-γ, IL-1β or an immunosuppressive molecule to the cDNA of a certain allergen (10), thus driving the immune response toward a Th1 direction.…”

Section: Discussionmentioning

confidence: 99%

Der p2‑A20 DNA vaccine attenuates allergic inflammation in mice with allergic rhinitis

Yang

et al. 2019

Mol Med Report

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Allergic rhinitis (AR) is a common disease that requires more convenient, safe and effective antigen-specific immunotherapies. The present study aimed to investigate the therapeutic effect of intranasal administration of a eukaryotic expression vector co-expressing Der p2 and A20 protein (pVAX1-Der p2-A20) on mice with allergic rhinitis. The pVAX1-Der p2-A20 vaccine was prepared and encapsulated into poly(L-lactide-co-glycolide) (PLGA) nanoparticles. An allergic rhinitis Balb/c mouse model was established through intraperitoneal sensitization with recombinant Der p2 and cholera toxin followed by intranasal challenge with recombinant Der p2. The treatment effect of the DNA vaccine on nasal allergic inflammation was evaluated, and serum IgE, sIgE, IgG and cytokine levels were determined by ELISA. The percentage of CD4+CD25+Foxp3+Tregs in the spleen was detected by flow cytometry. The DNA vaccine co-expressing Der p2 and A20 was successfully constructed and encapsulated into PLGA nanoparticles. Der p2-A20 DNA vaccine intranasal administration markedly ameliorated Der p2-induced nasal allergic inflammation. The serum Der p2-specific IgE, IL-4 and IL-13 expression levels were inhibited, while the Der p2-specific IgG1, IgG2a and IFN-γ expression levels in the serum and splenic CD4+CD25+Foxp3+Treg population were significantly increased after Der p2-A20 DNA vaccine treatment. These results indicated that the Der p2-A20 DNA vaccine alleviates nasal allergic inflammation and promotes splenic Treg population in mice with allergic rhinitis.

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Section: Discussionmentioning

confidence: 99%

Der p2‑A20 DNA vaccine attenuates allergic inflammation in mice with allergic rhinitis

Yang

et al. 2019

Mol Med Report

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“…This allows to escape of the risks of the injection and to improve the patients’ compliance. The intranasal use of Dermatophagoides pteronyssimus allergens entrapped in liposomes containing PC and cholesterol leads to lower IL-5 and IL-6 expression, higher expression of IL-10, IL-35, and TGFβ after the allergen provocation [ 86 ].…”

Section: Liposome-encapsulated Proteins and Peptidesmentioning

confidence: 99%

Topological Aspects of the Design of Nanocarriers for Therapeutic Peptides and Proteins

2019

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Supramolecular chemistry holds great potential for the design of versatile and safe carriers for therapeutic proteins and peptides. Nanocarriers can be designed to meet specific criteria for given application (exact drug, administration route, target tissue, etc.). However, alterations in the topology of formulation components can drastically change their activity. This is why the supramolecular topology of therapeutic nanoconstructions has to be considered. Herein, we discuss several topological groups used for the design of nanoformulations for peptide and protein delivery: modification of polypeptide chains by host-guest interactions; packaging of proteins and peptides into liposomes; complexation and conjugation with dendrimers. Each topological type has its own advantages and disadvantages, so careful design of nanoformulations is needed. Ideally, each case where nanomedicine is needed requires a therapeutic construction specially created for that taking into account features of the administration route, target tissue, or organ, properties of a drug, its bioavailability, etc. The wide number of studies in the field of protein delivery by supramolecular and nanocarriers for proteins and peptides evidence their increasing potential for different aspects of the innovative medicine. Although significant progress has been achieved in the field, there are several remaining challenges to be overcome in future.

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“…Compared to the complexity of previous attempts to produce allergen-bearing VLPs derived from the bacteriophage Qß [71][72][73][74][75][76][77], one of the great advantages of allergen-bearing BPs produced in this study, is that they are completely assembled within the host cell and secreted under their mature form between the plasmalemma and the plant cell wall.…”

Section: Plos Onementioning

confidence: 97%

Design, production and immunomodulatory potency of a novel allergen bioparticle

Gomord¹,

Stordeur²,

Fitchette³

et al. 2020

PLoS ONE

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Allergen immunotherapy (AIT) is the only disease-modifying treatment with evidence for sustained efficacy. However, it is poorly developed compared to symptomatic drugs. The main reasons come from treatment duration implying monthly injections during 3 to 5 years or daily sublingual use, and the risk of allergic side-effects. To become a more attractive alternative to lifelong symptomatic drug use, improvements to AIT are needed. Among the most promising new immunotherapy strategies is the use of bioparticles for the presentation of target antigen to the immune system as they can elicit strong T cell and B cell immune responses. Virus-like particles (VLPs) are a specific class of bioparticles in which the structural and immunogenic constituents are from viral origin. However, VLPs are ill-suited for use in AIT as their antigenicity is linked to structure. Recently, synthetic biology has been used to produce artificial modular bioparticles, in which supramolecular assemblies are made of elements from heterogeneous biological sources promoting the design and use of in vivo-assembling enveloped bioparticles for viral and non-viral antigens presentation. We have used a coiled-coil hybrid assembly for the design of an enveloped bioparticle (eBP) that present trimers of the Der p 2 allergen at its surface, This bioparticle was produced as recombinant and in vivo assembled eBPs in plant. This allergen biotherapeutic was used to demonstrate i) the capacity of plants to produce synthetic supramolecular allergen bioparticles, and ii) the immunomodulatory potential of naturally-assembled allergen bioparticles. Our results show that allergens exposed on eBPs induced a very strong IgG response consisting predominantly of IgG2a in favor of the TH1 response. Finally, our results demonstrate that rDer p 2 present on the surface of BPs show a very limited potential to stimulate the basophil degranulation of patient allergic to this allergen which is predictive of a high safety potential.

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Immunotherapeutic efficacy of liposome-encapsulated refined allergen vaccines against Dermatophagoides pteronyssinus allergy

Cited by 15 publications

References 92 publications

Der p2‑A20 DNA vaccine attenuates allergic inflammation in mice with allergic rhinitis

Der p2‑A20 DNA vaccine attenuates allergic inflammation in mice with allergic rhinitis

Topological Aspects of the Design of Nanocarriers for Therapeutic Peptides and Proteins

Design, production and immunomodulatory potency of a novel allergen bioparticle

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