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.

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

“… 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.…”

“…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.…”

“…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.…”

“…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].…”

“…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 .…”