Induction of bystander tolerance and immune deviation after Fel d 1 peptide immunotherapy

Moldaver, Daniel M.; Bharhani, Mantej S.; Rudulier, Christopher D.; Wattie, Jennifer; Inman, Mark D.; Larché, Mark

doi:10.1016/j.jaci.2018.03.023

Cited by 13 publications

(23 citation statements)

References 59 publications

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“…Many trials with T‐cell peptides have shown limited efficacy and/or led to nonimmediate allergic reactions during treatment although immunologic effects were demonstrated …”

Section: Current Managementmentioning

confidence: 99%

Keep the cat, change the care pathway: A transformational approach to managing Fel d 1, the major cat allergen

Satyaraj¹,

Wedner

Bousquet

2019

Allergy

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Background Allergies to cats are the most common animal‐origin allergy, and affect approximately 1 in 5 adults worldwide. The prevalence of allergy to furry animals has been increasing, and allergy to cats is a major risk factor for the development of asthma and rhinitis. The diagnosis of cat allergy is now well established. The exact significance of component‐resolved diagnosis in the diagnosis of cat allergy remains to be fully understood. Allergen avoidance is effective but often has a psychologic impact. Allergen immunotherapy is not well demonstrated. There is a need for innovative approaches to better manage cat allergens. Next‐generation care pathways for asthma and rhinitis will define the place of cat allergen avoidance. Methods and Results This manuscript, based on content presented at the European Academy of Allergy and Clinical Immunology Congress 2019, provides information on the prevalence and impact of cat allergies and the molecular biology of Fel d 1, the major cat allergen. Discussion The authors present the scientific basis of a novel care pathway that utilizes anti‐Fel d 1 IgY antibodies to safely and effectively neutralize Fel d 1 after its production by the cat but before human exposure. Conclusion Efficacy of a feline diet with an egg product ingredient containing anti‐Fel d 1 IgY antibodies was demonstrated in vitro, ex vivo, and in vivo, and further validated by a pilot exposure study involving cat‐allergic human participants.

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“…Many trials with T‐cell peptides have shown limited efficacy and/or led to nonimmediate allergic reactions during treatment although immunologic effects were demonstrated …”

Section: Current Managementmentioning

confidence: 99%

Keep the cat, change the care pathway: A transformational approach to managing Fel d 1, the major cat allergen

Satyaraj¹,

Wedner

Bousquet

2019

Allergy

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“…Consequently, the design of molecular AIT is based on the selection of clinically relevant allergens from any allergenic source. We cannot also exclude that AIT based on single molecules could trigger the activation of bystander Tregs, conferring protection against other allergens, as previously shown …”

Section: Discussionmentioning

confidence: 88%

Molecular approaches to allergen‐specific immunotherapy: Are we so far from clinical implementation?

Pechsrichuang

Jacquet

2020

Clin Experimental Allergy

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Conventional allergen-specific immunotherapy (AIT), based on administrations of allergen extracts, represents up to now the unique protocol for the desensitization of allergic patients. Whereas the effectiveness of AIT was evidenced for the treatment of allergic rhinitis and allergic asthma, such strategy remains experimental for food allergies up to now. However, important issues are commonly associated with AIT as the quality of natural allergen extracts, the long duration and adverse side-effects which negatively affect successful desensitization together with the patient compliance. The rapid progression of molecular allergology made possible the quest of safer, shorter and more effective immunotherapeutic approaches. The aim of this review was to provide an update on these different innovative recombinant derivatives including their efficacy but also their limitations. Despite promising preclinical and early clinical studies, the absence of convincing data in large phase III trials precludes so far the translation of these immunotherapeutic candidates into the clinic. K E Y W O R D S allergen-specific immunotherapy, blocking antibodies, clinical trial, efficacy, hypoallergenic, recombinant derivatives, safety, Treg Present AIT Delivery route SCIT SLIT Molecules Allergen extracts +/-Adjuvant Alum 26Abbreviations: 8x6Q2W, grass allergen peptides at 6 nmol at 2-wk intervals for a total of 8

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“…1,2 Peptides may have a short half-life after administration and need to be phagocytosed by DCs for presentation to T cells to exert their tolerogenic activity. Nonetheless, AIT requires large amounts of allergens that need to be administered over prolonged periods of time and treatment can induce severe side effects.…”

Section: Subcutaneous Immunotherapy Using Modified Phl P5a-derived Pementioning

confidence: 99%

“…Unfortunately, treatment response to peptide AIT is suboptimal for most allergens. 1,2 Peptides may have a short half-life after administration and need to be phagocytosed by DCs for presentation to T cells to exert their tolerogenic activity. We have previously designed a novel strategy to increase uptake and presentation of peptides by DCs, while also influencing their tolerogenic phenotype.…”

Section: Subcutaneous Immunotherapy Using Modified Phl P5a-derived Pementioning

confidence: 99%

“…These data indicate that CD16 high CD62L dim neutrophils are prone to phagocytose bacterial particles and induce oxidative burst (Figure 2 D).In 2012, Pillay et al 1 identified the existence of different neutrophil subsets. The CD16 high CD62L dim subset, regarded activated, exhibited T cell-suppressing capacities and decreased adherence to the endothelium during induced acute inflammatory conditions 2.…”

mentioning

confidence: 99%

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Subcutaneous immunotherapy using modified Phl p5a‐derived peptides efficiently alleviates allergic asthma in mice

Hesse

Feenstra

Ambrosini

et al. 2019

Allergy

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Induction of bystander tolerance and immune deviation after Fel d 1 peptide immunotherapy

Cited by 13 publications

References 59 publications

Keep the cat, change the care pathway: A transformational approach to managing Fel d 1, the major cat allergen

Keep the cat, change the care pathway: A transformational approach to managing Fel d 1, the major cat allergen

Molecular approaches to allergen‐specific immunotherapy: Are we so far from clinical implementation?

Subcutaneous immunotherapy using modified Phl p5a‐derived peptides efficiently alleviates allergic asthma in mice

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