Safety and Tolerability of a Novel Peptide-Based Immunotherapy for Peanut Allergy

Prickett, Sara; Hickey, Pascal; Bingham, Judy M.; Phan, Thi Hong Thu; Abramovitch, Jodie B.; Rolland, Jennifer M.; Smith, William B.; Hew, Mark; Hehir, Robyn E.O.

doi:10.1016/j.jaci.2018.12.975

Cited by 11 publications

(11 citation statements)

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“…However, the efficacy of desensitization is lower, particularly for EPIT. Peptide immunotherapy is another approach to minimize AEs by replacing whole allergens with short allergen peptides, which have a reduced capacity to crosslink IgE on the surface of mast cells and basophils ( 63 , 64 ). Preliminary findings from a clinical trial for PN allergy demonstrated no serious AEs ( 63 ).…”

Section: Current and Investigative Treatments For Food Allergymentioning

confidence: 99%

The Road Toward Transformative Treatments for Food Allergy

et al. 2022

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A series of landmark studies have provided conclusive evidence that the early administration of food allergens dramatically prevents the emergence of food allergy. One of the greatest remaining challenges is whether patients with established food allergy can return to health. This challenge is particularly pressing in the case of allergies against peanut, tree nuts, fish, and shellfish which are lifelong in most patients and may elicit severe reactions. The standard of care for food allergy is allergen avoidance and the timely administration of epinephrine upon accidental exposure. Epinephrine, and other therapeutic options like antihistamines provide acute symptom relief but do not target the underlying pathology of the disease. In principle, any transformative treatment for established food allergy would require the restoration of a homeostatic immunological state. This may be attained through either an active, non-harmful immune response (immunological tolerance) or a lack of a harmful immune response (e.g., anergy), such that subsequent exposures to the allergen do not elicit a clinical reaction. Importantly, such a state must persist beyond the course of the treatment and exert its protective effects permanently. In this review, we will discuss the immunological mechanisms that maintain lifelong food allergies and are, consequently, those which must be dismantled or reprogrammed to instate a clinically non-reactive state. Arguably, the restoration of such a state in the context of an established food allergy would require a reprogramming of the immune response against a given food allergen. We will discuss existing and experimental therapeutic strategies to eliminate IgE reactivity and, lastly, will propose outstanding questions to pave the road to the development of novel, transformative therapeutics in food allergy.

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Section: Current and Investigative Treatments For Food Allergymentioning

confidence: 99%

The Road Toward Transformative Treatments for Food Allergy

et al. 2022

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“…IL-4, IL-5, IL-31) thought to be implicated in control of those levels and other cell populations (eosinophils/basophils) implicated in allergic disease [29–33]. In addition, concerted efforts have ben made to improve the efficacy of allergen-induced attenuation of responses [7, 9–12, 15–18]. We have previously reported on the use of a novel therapy, aimed at manipulating self-reactive immune regulatory networks through deliberate perturbation of idiotype: anti-idiotype interactions, as a potential mechanism to attenuate several pathological immune reactions in rodents, including allergic sensitization to ovalbumin [19].…”

Section: Discussionmentioning

confidence: 99%

“…1b). It is worth stressing at this stage that the therapy used is one which occurs through mechanisms independent of the antigen used for sensitization, a feature of significant importance clinically when often the allergen cannot be identified and/or synthesized for allergen-specific desensitization [15–18].…”

Section: Discussionmentioning

confidence: 99%

“…Interestingly, there is evidence that the sublingual route of allergen delivery has less risk of severe adverse effects anyway [17], likely a result of functional difference between oral antigen-presenting cells (APCs) and Langerhans cells, their skin counterpart. Importantly, it is still unclear whether SLIT (or SCIT) must be given seasonally and or continuously for efficacy to be maintained [18].…”

Section: Introductionmentioning

confidence: 99%

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Mechanism(s) of prolonged attenuation of allergic responses after modulation of idiotypic regulatory network

Gorczynski

Maqbool²,

Hoffmann³

2019

Allergy Asthma Clin Immunol

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BackgroundWe showed previously that allergic reactivity to ovalbumin (OVA) could be regulated in mice following perturbation of immune networks using combinations of an immune Ig along with anti-idiotypic Ig. We have explored features of this regulation including: its persistence after cessation of administration of combined Igs; the ability of heterologous Igs to produce immunoregulation; a role for Treg induction in regulation; and the ability to attenuate responses in mice pre-sensitized to an allergic stimulus.MethodsBALB/c mice were sensitized to OVA. Mice also received 5 weekly injections of immune Ig or anti-idiotype Ig (at separate sites) from either homologous (mouse) or heterologous (human) sources. In the latter case pooled IVIG (given IM, hence hereafter IMIG) was used as a source of anti-idiotype Ig, and human anti-Tet as immune Ig. Injections of the Ig were given from the time of OVA sensitization (to attenuate development of immunity), or after pre-sensitization of mice (to attenuate existing allergic responses). All mice were assayed for development of OVA-specific serum IgE and IgG, as well as the production of OVA-induced IL-2, IL-4, IL-13, IL-31 and IL-33 in splenocytes cultured for 72 h. In studies examining possible mechanism(s) responsible for inhibition of immunity mice received, in addition to the Ig treatments described, infusion of depleting anti-CD4, and/or anti-CD8 antibodies, or a mAb to TNFSFR25, known to expand Tregs implicated in regulation of Allo immunity.ResultsCombinations of both heterologous and homologous immune Igs and anti-idiotype Igs attenuated OVA allergic responses in both naïve and pre-sensitized mice. This attenuation persisted in mice greater than 14 weeks after cessation of treatment with the Igs used. Finally, depletion of either CD4 or CD8 cells ameliorated the suppressive effect seen, while the combination of anti-CD4 and anti-CD8 essentially abolished suppression. Suppression was further enhanced by anti-TNFSFR25 mAb.ConclusionsWe conclude that the combine Ig treatment protocols used produced a long-lasting suppression of allergic immunity, even in pre-sensitized animals. The effects seem to depend upon induction and expansion of Tregs and represents a novel approach to treatment of allergic disease in humans and other animals.

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“…In a small Phase I study in Australia of 66 participants who underwent intradermal injection with a product consisting of several synthetic peptides derived from peanut allergens (PVX108; Aravax, Melbourne, Australia), the decreased allergenicity of peptide immunotherapy was demonstrated by a lack of basophil activation to the immunotherapy. 18 During the study, there were no serious adverse events and the AEs that did occur were mostly self-resolving injection site reactions. Although the study was limited by small sample size, the results indicated that peptide immunotherapy may prove advantageous in regards to reducing adverse reactions that may otherwise preclude use by an allergic individual.…”

Section: Future Directionsmentioning

confidence: 91%

Current Insights into Immunotherapy Approaches for Food Allergy

Macdougall¹,

Burks²,

Kim³

2021

ITT

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In the last decade, there has been increasing research dedicated to food immunotherapy to induce clinical desensitization and provide protection by increasing clinical reaction thresholds. Results from recent food immunotherapy studies with differing routes of administration (oral, sublingual, and epicutaneous) suggest that food immunotherapy can induce clinical desensitization with varying levels of safety, however lasting tolerance has not been demonstrated. Furthermore, treatment side effects and dosing logistics may make the therapies difficult for some supporting the need for alternative treatment approaches. Peptide immunotherapy and DNA vaccine approaches should in theory allow for safer administration by decreasing allergenicity but proof of their clinical efficacy and immunogenicity remains to be proven. Biologic agents may allow for increased safety and rapid up-dosing of immunotherapy with the added benefit of treating multiple allergens simultaneously.

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Safety and Tolerability of a Novel Peptide-Based Immunotherapy for Peanut Allergy

Cited by 11 publications

References 0 publications

The Road Toward Transformative Treatments for Food Allergy

The Road Toward Transformative Treatments for Food Allergy

Mechanism(s) of prolonged attenuation of allergic responses after modulation of idiotypic regulatory network

Current Insights into Immunotherapy Approaches for Food Allergy

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