The Safety and Efficacy of ALLERVAX CAT in Cat Allergic Patients

Maguire, Peter; Nicodemus, Christopher F.; Robinson, Donna; Aaronson, Don; Umetsu, Dale T.

doi:10.1006/clim.1999.4795

Cited by 123 publications

(85 citation statements)

References 28 publications

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“…It is of note that previous epitope-mapping studies identified immunodominant epitopes of Fel d 1 in chain 1, but not chain 2, of the molecule (32,33). It was largely as a result of those studies that a subsequent vaccine incorporated only chain 1 peptides (54). More recent studies examined the effects of injecting short peptides (ϳ16 mer) spanning chain 1 or both chains of the Fel d 1 molecule (9,13,55).…”

Section: Discussionmentioning

confidence: 99%

A Role for IL-10-Mediated HLA-DR7-Restricted T Cell-Dependent Events in Development of the Modified Th2 Response to Cat Allergen

Reefer¹,

Carneiro²,

Custis³

et al. 2004

The Journal of Immunology

125

123

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Although high dose exposure to inhaled cat allergen (Fel d 1) can cause a form of tolerance (modified Th2 response), the T cell mechanism for this phenomenon has not been studied. T cell responses to Fel d 1 were characterized in both allergic (IgEpos) and modified Th2 (IgEnegIgGpos) responders as well as serum Ab-negative controls (IgEnegIgGneg). Fel d 1 stimulated high levels of IL-10 in PBMC cultures from all individuals, with evidence of Th2 and Th1 cytokine skewing in allergic and control subjects, respectively. Using overlapping peptides, epitopes at the N terminus of Fel d 1 chain 2 were shown to stimulate strong T cell proliferation and to preferentially induce IL-10 (peptide 2:1 (P2:1)) or IFN-γ (P2:2) regardless of the allergic status of the donor. Injection of cat extract during conventional immunotherapy stimulated expansion of IL-10- and IFN-γ-producing chain 2 epitope-specific T cells along with increased Fel d 1-specific serum IgG and IgG4 Ab. Six of 12 modified responders expressed the major HLA-DRB1 allele, *0701, and both P2:1 and P2:2 were predicted ligands for this allele. Cultures from DR7-positive modified responders produced the highest levels of IL-10 to P2:1 in addition to other major and minor epitopes within chains 1 and 2. In the presence of anti-IL-10 mAb, both T cell proliferation and IFN-γ production were enhanced in a Fel d 1- and epitope-specific manner. We conclude that IL-10-producing T cells specific for chain 2 epitopes are relevant to tolerance induction, and that DR7-restricted recognition of these epitopes favors a modified Th2 response.

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Section: Discussionmentioning

confidence: 99%

A Role for IL-10-Mediated HLA-DR7-Restricted T Cell-Dependent Events in Development of the Modified Th2 Response to Cat Allergen

Reefer¹,

Carneiro²,

Custis³

et al. 2004

The Journal of Immunology

125

123

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“…Since then, the application of allergen-derived peptides containing T cell epitopes has been tested in several clinical studies and indeed no immediate type symptoms were elicited. However, treatment with peptides of the major cat allergen, Fel d 1, was still associated with adverse events, primarily the late-onset symptoms of rhinitis, asthma and pruritus [88][89][90][91]. The incidence of late adverse events was related to both peptide dose and the severity of disease [9,92,93].…”

Section: Past and Present Attempts For The Improvement Of Allergen-spmentioning

confidence: 99%

Developments in allergen‐specific immunotherapy: from allergen extracts to allergy vaccines bypassing allergen‐specific immunoglobulin E and T cell reactivity

Focke

Swoboda

Marth

et al. 2010

Clin Experimental Allergy

101

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SummaryAllergen-specific immunotherapy (SIT) is the only specific and disease-modifying approach for the treatment of allergy but several disadvantages have limited its broad applicability. We argue that the majority of the possible disadvantages of SIT such as unwanted effects, poor efficacy and specificity as well as inconvenient application are related to the poor quality of natural allergen extracts, which are the active ingredients of all currently available allergy vaccines. Because of the progress made in the field of molecular allergen characterization, new allergy vaccines based on recombinant allergens, recombinant hypoallergenic allergen derivatives and allergen-derived T cell peptides have entered clinical testing and hold promise to reduce the side-effects and to increase the specificity as well as the efficacy of SIT. Here, we present a refined immunotherapy concept, which is based on the use of peptides derived from allergen surfaces that exhibit reduced, allergen-specific IgE as well as T cell reactivity. These peptides when fused to non-allergenic carriers give rise to allergen-specific protective IgG responses with T cell help from a non-allergenic carrier molecule. We summarize the experimental data demonstrating that such peptide vaccines can bypass allergen-specific IgE as well as T cell activation and may be administered at high doses without IgE-and T cell-mediated side-effects. Should these peptide vaccines prove efficacious and safe in clinical trials, it may become possible to develop convenient, safe and broadly applicable forms of SIT as true alternatives to symptomatic, drug-based allergy treatment.

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“…As recognition of allergen-derived peptides by T cells is dependent on presentation in the context of appropriate MHC molecules, the limited clinical benefit previously observed with peptide immunotherapy may be in part explained by the fact that MHC restriction was not accounted for in the original peptide design [39, 40]. However, the complexity of providing an exhaustive analysis of T cell epitope binding is illustrated by the description of more than 200 molecules expressed by the HLA-DRB 1 locus (the most abundant class II molecules at the surface of antigen-presenting cells) [41].…”

Section: Selection Of Peptide Epitopes For Immunotherapymentioning

confidence: 99%

“…In a randomized double-blind placebo-controlled study, Maguire et al [40]investigated the effect of IPC 1 and IPC 2 peptides (derived from the sequence of the major cat allergen Fel d 1) in 133 cat-allergic patients chronically exposed to cats or who had previously failed conventional cat immunotherapy. Eight subcutaneous injections of IPC 1 and IPC 2 were administered at two doses (75 and 750 µg), and the efficacy of therapy was assessed 3 and 8 weeks following the onset of treatment.…”

Section: Clinical Trials Of Allergen-specific Peptide Immunotherapymentioning

confidence: 99%

Peptide-Mediated Immune Responses in Specific Immunotherapy

Haselden

Kay

Larché³

2000

Int Arch Allergy Immunol

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Conventional immunotherapy using whole allergen extracts has been shown to be an effective, disease-modifying treatment in carefully selected patients with allergic conjunctivo-rhinitis, asthma and bee and wasp venom hypersensitivity. However, this form of therapy is associated with the risk of systemic anaphylaxis, which, when severe, can be life threatening. A potentially significant reduction in the incidence of IgE-mediated events during immunotherapy may be achieved by the use of short peptides corresponding to T cell epitopes which, by virtue of their size, are incapable of cross-linking allergen-specific IgE bound to the surface of mast cells and basophils. Initial clinical studies have demonstrated degrees of efficacy which have, in some cases, been associated with adverse events occurring immediately or several hours after peptide administration. Preliminary data from studies employing shorter peptides (20 amino acids or less) suggest that improved efficacy may be achieved by using peptides of defined major histocompatibility complex-binding specificity administered in an incremental dose fashion comparable to conventional immunotherapy. This review will discuss the concept of peptide immunotherapy and the implications of recent studies.

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The Safety and Efficacy of ALLERVAX CAT in Cat Allergic Patients

Cited by 123 publications

References 28 publications

A Role for IL-10-Mediated HLA-DR7-Restricted T Cell-Dependent Events in Development of the Modified Th2 Response to Cat Allergen

A Role for IL-10-Mediated HLA-DR7-Restricted T Cell-Dependent Events in Development of the Modified Th2 Response to Cat Allergen

Developments in allergen‐specific immunotherapy: from allergen extracts to allergy vaccines bypassing allergen‐specific immunoglobulin E and T cell reactivity

Peptide-Mediated Immune Responses in Specific Immunotherapy

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