Prevention of allergy by virus‐like nanoparticles (<scp>VNP</scp>) delivering shielded versions of major allergens in a humanized murine allergy model

Kratzer, Bernhard; Köhler, Cordula; Höfer, Sandra; Smole, Ursula; Trapin, Doris; Iturri, Jagoba; Pum, Dietmar; Kienzl, Philip; Elbe‐Bürger, Adelheid; Gattinger, Pia; Mittermann, Irene; Linhart, Birgit; Gadermaier, Gabriele; Jahn‐Schmid, Beatrice; Neunkirchner, Alina; Valenta, Rudolf; Pickl, Winfried F.

doi:10.1111/all.13573

Cited by 37 publications

(32 citation statements)

References 67 publications

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“… and Kratzer et al. could demonstrate that allergens displayed on the surface of VNP induced much weaker degranulation of IgE‐sensitized effector cells when compared to equimolar concentrations of the respective soluble allergens (Fel d 1 and Art v 1) . From the above it can be argued that the mere cell surface association of an otherwise soluble allergen might render it hypoallergenic.…”

Section: Vnp‐based Strategies For Allergy Treatmentmentioning

confidence: 97%

“…For that purpose, they relied on the full-length major mugwort pollen allergen Art v 1 fused to the MoMLV matrix protein p15, which targets any fusion partner, so also the allergen, to the inside of the MoMLV VNP envelope. In a new mouse model of mugwort allergy [105], these authors could show that such VNP preparations are non-anaphylactogenic and non-sensitizing (IgE inducing) but instead able to induce tolerance if applied intranasally [91]. To corroborate these finding, the authors plan to screen more patient sera and also plan to perform basophil activation tests with whole blood of mugwort allergic individuals.…”

Section: Vnp Eliciting Allergen-dependent Immunomodulationmentioning

confidence: 99%

“…However, this strategy also increases the risk for adverse reactions in already sensitized individuals, since allergen‐VNP might lead to IgE cross‐linking on effector cells resulting in mediator release and anaphylaxis. Until today, only a small collection of full‐length allergens have been attached/targeted to the surface of VNP and subsequently evaluated, which include the major house dust mite allergen Der p 1 , the major cat dander allergen Fel d 1 , and the major mugwort pollen allergen Art v 1 . Interestingly, both Engeroff et al.…”

Section: Vnp‐based Strategies For Allergy Treatmentmentioning

confidence: 99%

“…However, this strategy also increases the risk for adverse reactions in already sensitized individuals, since allergen-VNP might lead to IgE cross-linking on effector cells resulting in mediator release and anaphylaxis. Until today, only a small collection of full-length allergens have been attached/targeted to the surface of VNP and subsequently evaluated, which include the major house dust mite allergen Der p 1 [88], the major cat dander allergen Fel d 1 [89,90], and the major mugwort pollen allergen Art v 1 [91]. Interestingly, both Engeroff et al [89] and Kratzer et al [91] could demonstrate that allergens displayed on the surface of VNP induced much weaker degranulation of IgE-sensitized effector cells when compared to equimolar concentrations of the respective soluble allergens (Fel d 1 and Art v 1) [89,91].…”

Section: Vnp Eliciting Allergen-dependent Immunomodulationmentioning

confidence: 99%

“…Possible disadvantages of such technology lie, e.g., in the potentially imprecise targeting of the VNP delivered systemically to the “wrong,” immunoactivating APC and/or the instability of the enveloped viral particle, which, upon undesired disassembly would release full‐length allergens that may lead to effector cell activation and anaphylaxis. . However, these potential caveats can be omitted by using strict T cell epitopes of major allergens, which are otherwise unable to crosslink IgE on allergen‐specific B cells or on sensitized effector cells .…”

Section: Vnp‐based Strategies For Allergy Treatmentmentioning

confidence: 99%

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All the small things: How virus‐like particles and liposomes modulate allergic immune responses

et al. 2019

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Recent years have seen a dramatic increase in the range of applications of virus‐like nanoparticle (VNP)‐ and liposome‐based antigen delivery systems for the treatment of allergies. These platforms rely on a growing number of inert virus‐backbones or distinct lipid formulations and intend to engage the host's innate and/or adaptive immune system by virtue of their co‐delivered immunogens. Due to their particulate nature, VNP and liposomal preparations are also capable of breaking tolerance against endogenous cytokines, Igs, and their receptors, allowing for the facile induction of anti‐cytokine, anti‐IgE, or anti‐FcεR antibodies in the host. We here discuss the “pros and cons” of inducing such neutralizing autoantibodies. Moreover, we cover another major theme of the last years, i.e., the engineering of non‐anaphylactogenic particles and the elucidation of the parameters relevant for the specific trafficking and processing of such particles in vivo. Finally, we put the various technical advances in VNP‐ and liposome‐research into (pre‐)clinical context by referring and critically discussing the relevant studies performed to treat allergic diseases.

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Section: Vnp‐based Strategies For Allergy Treatmentmentioning

confidence: 97%

Section: Vnp Eliciting Allergen-dependent Immunomodulationmentioning

confidence: 99%

Section: Vnp‐based Strategies For Allergy Treatmentmentioning

confidence: 99%

Section: Vnp Eliciting Allergen-dependent Immunomodulationmentioning

confidence: 99%

Section: Vnp‐based Strategies For Allergy Treatmentmentioning

confidence: 99%

See 3 more Smart Citations

All the small things: How virus‐like particles and liposomes modulate allergic immune responses

et al. 2019

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Nanoparticles in Allergen‐Delivery Systems for Allergen‐Specific Immunotherapy

Lee,

Chandrawati,

Lee

2024

Advanced Therapeutics

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Allergen‐specific immunotherapy (AIT) has demonstrated its ability to induce desensitization, resulting in reduced allergen‐specific immunoglobulin E (sIgE) accompanied by increased clinical thresholds. However, ensuring safety during therapy, especially with oral immunotherapy, and achieving long‐term tolerance continue to be significant challenges. To address these issues, a concept of nanoencapsulation of allergens has emerged. This paper reviews biodegradable and non‐biodegradable nanoparticles as an allergen‐delivery system, as well as adjuvants for the improvement of the efficacy of AIT. Of all the nanoparticles reviewed, polymethyl methacrylate (PMMA) and chitosan are the most popular nanoparticles for encapsulating macromolecular allergens for oral immunotherapy. Although poly(lactic‐co‐glycolic acid) (PLGA) demonstrates higher stability in the gastrointestinal environment and allergen‐loaded PLGA attenuates the sIgE antibody binding in a murine model, it has inconsistent loading capacity and is difficult to reproduce. Studies on biodistribution, pharmacokinetics, and pharmacodynamics of nanoparticles, however, should be highlighted to ensure the long‐term safety profile of utilizing nanoparticles in immunotherapy. In this regard, encapsulation efficiency and release behavior of allergens from nanoparticles are important components in predicting the safety and efficacy of treatments. The stability, reproducibility, and scalability of encapsulated allergens should also be considered for the translation to clinical applications.

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Biomaterial Strategies for Selective Immune Tolerance: Advances and Gaps

2023

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Autoimmunity and allergies affect a large number of people across the globe. Current approaches to these diseases target cell types and pathways that drive disease, but these approaches are not cures and cannot differentiate between healthy cells and disease‐causing cells. New immunotherapies that induce potent and selective antigen‐specific tolerance is a transformative goal of emerging treatments for autoimmunity and serious allergies. These approaches offer the potential of halting—or even reversing—disease, without immunosuppressive side effects. However, translating successful induction of tolerance to patients is unsuccessful. Biomaterials offer strategies to direct and maximize immunological mechanisms of tolerance through unique capabilities such as codelivery of small molecules or signaling molecules, controlling signal density in key immune tissues, and targeting. While a growing body of work in this area demonstrates success in preclinical animal models, these therapies are only recently being evaluated in human trials. This review will highlight the most recent advances in the use of materials to achieve antigen‐specific tolerance and provide commentary on the current state of the clinical development of these technologies.

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Prevention of allergy by virus‐like nanoparticles (VNP) delivering shielded versions of major allergens in a humanized murine allergy model

Abstract: Virus-like nanoparticles represent a novel and versatile platform for the in vivo delivery of allergens to selectively target T cells and prevent allergies without inducing allergic reactions or allergic sensitization.

Cited by 37 publications

References 67 publications

All the small things: How virus‐like particles and liposomes modulate allergic immune responses

All the small things: How virus‐like particles and liposomes modulate allergic immune responses

Nanoparticles in Allergen‐Delivery Systems for Allergen‐Specific Immunotherapy

Biomaterial Strategies for Selective Immune Tolerance: Advances and Gaps

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