Plant‐based enveloped Ara h 2 bioparticles display exceptional hypo‐allergenicity

Abstract

Since the early nineties several approaches have been tested to develop safe and effective allergen immunotherapy (AIT) for the treatment of peanut allergy, starting with subcutaneous AIT with aqueous extract, followed by hypo-allergenic major allergens produced in bacteria that were administered rectally. These approaches were abandoned, mainly because of too many severe side-effects.Other administration routes that are considered to be safer, like sublingual and epicutaneous, have not yet reached the market. The only treatment that did receive market authorization is oral immunotherapy (OIT). It is effective for desensitization, disappointing for sustained efficacy, and side-effects occur frequently. 1 Furthermore, the most sensitive patients being at risk of severe life-threatening allergic reactions are unlikely to be helped with this approach, as side-effects may include severe anaphylaxis. 2 Therefore, there is an urgent need to provide all patients, including the severest ones, with a safe and effective treatment. Recently, nano-and micro-particulate strategies, such as virus-like particles, have been proposed as potentially safe and effective approaches. For example, a virus-based particle Centre", and a grant from the National Institute of Allergy and

Phase 1 trial supports safety and mechanism of action of peptide immunotherapy for peanut allergy

“…Safety of PVX108 was further supported by the absence of allergen‐specific IgE increases following treatment (attributed to the lack of IgE epitopes within PVX108) and the inability of PVX108 to activate peanut‐sensitized basophils ex vivo ( n = 185). Despite widespread attempts to generate hypo‐allergenic peanut‐based products, no other approach has shown a comparable inability to activate basophils across an equivalent concentration range as shown for PVX108 53–56 . In addition to its safety profile, pre‐clinical testing showed PVX108 bound a wide range of HLA II molecules, (collectively expressed by >99.5% of the population) and induced dose‐related T‐cell responses, confirming that these binding properties translate to physiologically relevant responses in target T cells.…”

“…52 . [53][54][55][56] In addition to its safety profile, pre-clinical testing TA B L E 2 Summary of all adverse events by treatment group. Abbreviations: (%) 1 , percentage of participants experiencing an adverse event; (%) 2 , percentage of adverse events; n 1 , number of participants experiencing an adverse event; n 2 , number of adverse events; TEAE, treatment emergent adverse event.…”

Exploring the Potentiality of a Plant Platform for Monoclonal Antibody Production in Veterinary Medicine

“…Many studies have illustrated that plants have the capacity to produce high-quality recombinant antibodies [ 19 , 34 , 35 , 36 ] and also biopharmaceuticals designed for new therapeutic approaches [ 37 , 38 , 39 ]. Therefore, plant-made mAbs have potential to be a viable alternative to their counterpart produced in mammalian cells [ 25 ].…”

Plant‐produced Der p 2‐bearing bioparticles activate Th1/Treg‐related activation patterns in dendritic cells irrespective of the allergic background

“…This suggests that multivalent high‐density allergen presentation on e BPs creates hypoallergenicity. Earlier reports based on e BP‐rFel d 1/‐rAra h 2 show even (far) higher reductions in basophil degranulation 4,5 . It can be hypothesized that IgE binding capacities and related effector cell activation might be linked to the localization of the respective dominant IgE epitopes, which might either be exposed or shielded off due to the one‐directional allergen anchorage on the e BP surface 5 .…”

“…Earlier reports based on eBP-rFel d 1/-rAra h 2 show even (far) higher reductions in basophil degranulation. 4,5 It can be hypothesized that IgE binding capacities and related effector cell activation might be linked to the localization of the respective dominant IgE epitopes, which might either be exposed or shielded off due to the one-directional allergen anchorage on the eBP surface. 5 Other factors contributing to deviating allergenic potency might include differences in the density of surface expression as well as size and charge of the eBPs.…”