Immunization of cats to induce neutralizing antibodies against Fel d 1, the major feline allergen in human subjects

Thoms, Franziska; Jennings, Gary T.; Maudrich, Melanie; Vogel, Monique; Haas, Stefanie; Zeltiņš, Andris; Hofmann‐Lehmann, Regina; Riond, Barbara; Grossmann, Jonas; Hunziker, Peter; Fettelschoss‐Gabriel, Antonia; Senti, Gabriela; Kündig, Thomas M.; Bachmann, Martin F.

doi:10.1016/j.jaci.2019.01.050

Cited by 49 publications

(56 citation statements)

References 46 publications

(52 reference statements)

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“…Novel strategies have been developed to treat Fel d 1‐induced allergy in human subjects by immunizing cats against their own major allergen . A conjugate vaccine consisting of recombinant Fel d 1 and a virus‐like particle derived from the cucumber mosaic virus containing the tetanus toxin‐derived universal T‐cell epitope tt830‐843 (CuMV TT ) was used to immunize cats.…”

Section: Neutralizing Fel D 1 At Its Sourcementioning

confidence: 99%

“…The induced anti-Fel d 1 antibodies were of high affinity and exhibited a strong neutralization ability tested both in vitro and in vivo. A reduction in the endogenous allergen level and a reduced allergenicity of tear samples were observed 120. However, clinical studies are needed to confirm the approach.…”

mentioning

confidence: 98%

“…Pezzali et al119 postulated that dietary modification to reduce sebum production may lower Fel d 1 production by cats: possible modifications included isoflavones and phytoestrogens to reduce androgen production; reducing the omega-6/omega-3 fatty acid ratio in the diet; and reducing the glycemic index of the cat's diet by lowering carbohydrate levels 119. However, the clinical efficacy of their proposed modifications has not, to the authors' knowledge, been investigated.Novel strategies have been developed to treat Fel d 1-induced allergy in human subjects by immunizing cats against their own major allergen 120. A conjugate vaccine consisting of recombinant Fel d 1 and a virus-like particle derived from the cucumber mosaic virus containing the tetanus toxin-derived universal T-cell epitope tt830-843 (CuMV TT ) was used to immunize cats.…”

mentioning

confidence: 99%

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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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Section: Neutralizing Fel D 1 At Its Sourcementioning

confidence: 99%

mentioning

confidence: 98%

mentioning

confidence: 99%

See 1 more Smart Citation

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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“…challenge with soluble rFel d 1 [90]. Recently, CuMV expressing Fel d 1 and containing the tetanus toxin-derived universal T cell helper epitope TT830-843 have been devised and applied in cats to induce autoantibodies against their major cat allergen Fel d 1 [93,94]. The induced blocking autoantibodies displayed high affinity for Fel d 1 and reduced Fel d 1-levels systemically, i.e., also in tear fluid of animals, which, apart from saliva, is a rich source of that secretoglobulin [93,94] Since full-length allergens introduced systemically might induce anaphylaxis in sensitized individuals, alternative strategies restricted to T or B cell epitopes have been developed.…”

Section: Vnp Eliciting Allergen-dependent Immunomodulationmentioning

confidence: 99%

“…Recently, CuMV expressing Fel d 1 and containing the tetanus toxin-derived universal T cell helper epitope TT830-843 have been devised and applied in cats to induce autoantibodies against their major cat allergen Fel d 1 [93,94]. The induced blocking autoantibodies displayed high affinity for Fel d 1 and reduced Fel d 1-levels systemically, i.e., also in tear fluid of animals, which, apart from saliva, is a rich source of that secretoglobulin [93,94] Since full-length allergens introduced systemically might induce anaphylaxis in sensitized individuals, alternative strategies restricted to T or B cell epitopes have been developed. Along those lines, the p1 protein of the yeast retrotransposon Ty, which has been shown to spontaneously assemble into VNP previously [95], has been conjugated with T cell epitopes of the mite allergen Der p 1 to devise Der p 1 Ty-VNP, which were used to immunize mice intraperitoneally.…”

Section: Vnp Eliciting Allergen-dependent Immunomodulationmentioning

confidence: 99%

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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The holo beta‐lactoglobulin lozenge reduces symptoms in cat allergy—Evaluation in an allergen exposure chamber and by titrated nasal allergen challenge

Bergmann

Raab²,

Graessel

et al. 2023

Clinical & Translational All

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Background The allergists´ tool box in cat allergy management is limited. Clinical studies have shown that holo beta‐lactoglobulin (holoBLG) can restore micronutritional deficits in atopic immune cells and alleviate allergic symptoms in a completely allergen‐nonspecific manner. With this study, we aimed to provide proof of principle in cat allergy. Methods A novel challenge protocol for cat allergy in a standardized ECARF allergen exposure chamber (AEC) was developed. In an open pilot study (NCT05455749), patients with clinically relevant cat allergy were provoked with cat allergen for 120 min in the AEC before and after a 3‐month intervention phase (holoBLG lozenge 2x daily). Nasal, conjunctival, bronchial, and pruritus symptoms were scored every 10 min– constituting the total symptom score (TSS). Peak nasal inspiratory flow (PNIF) was measured every 30 min. In addition, a titrated nasal provocation test (NPT) was performed before and after the intervention. Primary endpoint was change in TSS at the end of final exposure compared to baseline. Secondary endpoints included changes in PNIF, NPT, and occurrence of late reactions up to 24 h after exposure. Results 35 patients (mean age: 40 years) completed the study. Compared to baseline, holoBLG supplementation resulted in significant improvement in median TSS of 50% (p < 0.001), as well as in median nasal flow by 20 L/min (p = 0.0035). 20% of patients reported late reactions after baseline exposure, but 0% after the final exposure. Conclusions Cat allergic patients profited from targeted micronutrition with the holoBLG lozenge. As previously seen in other allergies, holoBLG supplementation also induced immune resilience in cat allergies, resulting in significant symptom amelioration.

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Immunization of cats to induce neutralizing antibodies against Fel d 1, the major feline allergen in human subjects

Cited by 49 publications

References 46 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

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

The holo beta‐lactoglobulin lozenge reduces symptoms in cat allergy—Evaluation in an allergen exposure chamber and by titrated nasal allergen challenge

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