Skip to main content
OSTI.GOVU.S. Department of Energy Office of Scientific and Technical Information
U.S. Department of Energy
Office of Scientific and Technical Information
 

Treating cat allergy with monoclonal IgG antibodies that bind allergen and prevent IgE engagement

Journal Article · · Nature Communications
 [1];  [2];  [2];  [2];  [2];  [2];  [2];  [3];  [2];  [2];  [2];  [2];  [2];  [2];  [2];  [2];  [2];  [2];  [2];  [2] more »;  [2];  [2];  [2] « less
  1. Regeneron Pharmaceuticals Inc., Tarrytown, NY (United States); DOE/OSTI
  2. Regeneron Pharmaceuticals Inc., Tarrytown, NY (United States)
  3. Regeneron Pharmaceuticals Inc.,Tarrytown, NY (United States)
+ Show Author Affiliations
Acute allergic symptoms are caused by allergen-induced crosslinking of allergen-specific immunoglobulin E (IgE) bound to Fc-epsilon receptors on effector cells. Desensitization with allergen-specific immunotherapy (SIT) has been used for over a century, but the dominant protective mechanism remains unclear. One consistent observation is increased allergen-specific IgG, thought to competitively block allergen binding to IgE. Here we show that the blocking potency of the IgG response to Cat-SIT is heterogeneous. Next, using two potent, pre-selected allergen-blocking monoclonal IgG antibodies against the immunodominant cat allergen Fel d 1, we demonstrate that increasing the IgG/IgE ratio reduces the allergic response in mice and in cat-allergic patients: a single dose of blocking IgG reduces clinical symptoms in response to nasal provocation (ANCOVA, p = 0.0003), with a magnitude observed at day 8 similar to that reported with years of conventional SIT. This study suggests that simply augmenting the blocking IgG/IgE ratio may reverse allergy.
Research Organization:
Lawrence Berkeley National Laboratory (LBNL), Berkeley, CA (United States)
Sponsoring Organization:
USDOE Office of Science (SC), Basic Energy Sciences (BES). Scientific User Facilities Division
Grant/Contract Number:
AC02-05CH11231
OSTI ID:
1624085
Journal Information:
Nature Communications, Journal Name: Nature Communications Journal Issue: 1 Vol. 9; ISSN 2041-1723
Publisher:
Nature Publishing GroupCopyright Statement
Country of Publication:
United States
Language:
English

References (73)

Effect of Subcutaneous Dupilumab on Nasal Polyp Burden in Patients With Chronic Sinusitis and Nasal Polyposis: A Randomized Clinical Trial journal February 2016
T Cell Epitope Peptide Therapy for Allergic Diseases journal January 2016
A long-term follow-up study of hyposensitization with immunoblotting journal June 1990
Enlarging the repertoire of therapeutic monoclonal antibodies platforms: domesticating half molecule exchange to produce stable IgG4 and IgG1 bispecific antibodies journal December 2014
Passive immunization with allergen-specific IgG antibodies for treatment and prevention of allergy journal June 2013
Dose dependence and time course of the immunologic response to administration of standardized cat allergen extract journal December 2004
Anti-IgE (omalizumab) inhibits late-phase reactions and inflammatory cells after repeat skin allergen challenge journal September 2005
Fluticasone furoate nasal spray reduces the nasal-ocular reflex: A mechanism for the efficacy of topical steroids in controlling allergic eye symptoms journal June 2009
Effects of omalizumab on basophil and mast cell responses using an intranasal cat allergen challenge journal April 2010
Development and preliminary clinical evaluation of a peptide immunotherapy vaccine for cat allergy journal January 2011
A hypoallergenic cat vaccine based on Fel d 1–derived peptides fused to hepatitis B PreS journal June 2011
SQ-standardized sublingual grass immunotherapy: Confirmation of disease modification 2 years after 3 years of treatment in a randomized trial journal March 2012
Dupilumab improves the molecular signature in skin of patients with moderate-to-severe atopic dermatitis journal December 2014
Efficacy of 2 months of allergen-specific immunotherapy with Bet v 1–derived contiguous overlapping peptides in patients with allergic rhinoconjunctivitis: Results of a phase IIb study journal July 2016
The IgE-facilitated allergen binding (FAB) assay: Validation of a novel flow-cytometric based method for the detection of inhibitory antibody responses journal December 2006
Flow cytometry for basophil activation markers: The measurement of CD203c up-regulation is as reliable as CD63 expression in the diagnosis of cat allergy journal March 2007
Severe asthma and asthma-chronic obstructive pulmonary disease syndrome journal December 2016
A chimeric human-cat fusion protein blocks cat-induced allergy journal March 2005
Integrated signalling pathways for mast-cell activation journal February 2006
Dupilumab Treatment in Adults with Moderate-to-Severe Atopic Dermatitis journal July 2014
Effect of Avoidance on Peanut Allergy after Early Peanut Consumption journal April 2016
Mice with megabase humanization of their immunoglobulin genes generate antibodies as efficiently as normal mice journal March 2014
Successful immunotherapy induces previously unidentified allergen-specific CD4+ T-cell subsets journal January 2016
The Crystal Structure of the Major Cat Allergen Fel d 1, a Member of the Secretoglobin Family journal July 2003
An essential role for RasGRP1 in mast cell function and IgE-mediated allergic response journal December 2006
Mechanisms of immunotherapy: IgG revisited journal January 2004
Features and development of Coot journal March 2010
Immunological changes during specific immunotherapy of grass pollen allergy: reduced lymphoproliferative responses to allergen and shift from TH2 to TH1 in T-cell clones specific for Phi p 1, a major grass pollen allergen journal September 1997
When allergies complicate allergies journal May 2005
Simultaneous exposure of several allergens has an additive effect on multisensitized basophils journal November 2006
Recombinant Marker Allergens: Diagnostic Gatekeepers for the Treatment of Allergy journal January 2002
Renaissance of the Blocking Antibody Concept in Type I Allergy journal January 2003
Role of the Major Allergen (Fel d I) in Patients Sensitized to Cat Allergens journal January 1993
Epitope-specific T cell tolerance to phospholipase A2 in bee venom immunotherapy and recovery by IL-2 and IL-15 in vitro. journal October 1996
T Cell Epitope Immunotherapy Induces a CD4+ T Cell Population with Regulatory Activity journal March 2005
Clinical efficacy and immune regulation with peanut oral immunotherapy text January 2009
An integrated analysis of the efficacy of fluticasone furoate nasal spray versus placebo on the nasal symptoms of perennial allergic rhinitis journal May 2013
Effect of 2 Years of Treatment With Sublingual Grass Pollen Immunotherapy on Nasal Response to Allergen Challenge at 3 Years Among Patients With Moderate to Severe Seasonal Allergic Rhinitis: The GRASS Randomized Clinical Trial journal February 2017
Effect of Omalizumab on Symptoms of Seasonal Allergic RhinitisA Randomized Controlled Trial journal December 2001
Isolation and partial characterization of the major allergen from Japanese cedar () pollen journal January 1983
Onset and duration of action of levocabastine nasal spray in atopic patients under nasal challenge conditions journal April 1999
Prophylactic Inoculation Against hay Fever journal June 1911
Dupilumab efficacy and safety in adults with uncontrolled persistent asthma despite use of medium-to-high-dose inhaled corticosteroids plus a long-acting β2 agonist: a randomised double-blind placebo-controlled pivotal phase 2b dose-ranging trial journal July 2016
Mechanisms, safety and efficacy of a B cell epitope-based vaccine for immunotherapy of grass pollen allergy journal September 2016
Allergen skin tests and free IgE levels during reduction and cessation of omalizumab therapy journal February 2008
Grass pollen immunotherapy: IL-10 induction and suppression of late responses precedes IgG4 inhibitory antibody activity journal May 2008
Clinical efficacy and immune regulation with peanut oral immunotherapy journal August 2009
The effects of an anti–IL-13 mAb on cytokine levels and nasal symptoms following nasal allergen challenge journal October 2011
Development and characterization of a recombinant, hypoallergenic, peptide-based vaccine for grass pollen allergy journal May 2015
Vaccine development for allergen-specific immunotherapy based on recombinant allergens and synthetic allergen peptides: Lessons from the past and novel mechanisms of action for the future journal February 2016
Treatment effect of sublingual immunotherapy tablets and pharmacotherapies for seasonal and perennial allergic rhinitis: Pooled analyses journal October 2016
Flexible IgE epitope-containing domains of Phl p 5 cause high allergenic activity journal October 2017
PARP1 exhibits enhanced association and catalytic efficiency with γH2A.X-nucleosome journal December 2019
Long-Term Clinical Efficacy of Grass-Pollen Immunotherapy journal August 1999
Dupilumab Treatment in Adults with Moderate-to-Severe Atopic Dermatitis journal July 2014
Effect of Avoidance on Peanut Allergy after Early Peanut Consumption journal April 2016
Two Phase 3 Trials of Dupilumab versus Placebo in Atopic Dermatitis journal December 2016
A double-blind, placebo-controlled immunotherapy dose-response study with standardized cat extract journal January 2003
Synthetic antibodies for specific recognition and crystallization of structured RNA journal December 2007
Precise and in situ genetic humanization of 6 Mb of mouse immunoglobulin genes journal March 2014
The Crystal Structure of the Major Cat Allergen Fel d 1, a Member of the Secretoglobin Family journal July 2003
Mediators of inflammation in the early and the late phase of allergic rhinitis journal January 2004
Phaser crystallographic software journal July 2007
Features and development of Coot journal March 2010
IgG-mediated down-regulation of IgE bound to mast cells: a potential novel mechanism of allergen-specific desensitization journal December 2013
Hypoallergenic derivatives of Fel d 1 obtained by rational reassembly for allergy vaccination and tolerance induction journal May 2014
Local and systemic effects of cat allergen nasal provocation journal February 2015
Fel d 1-derived synthetic peptide immuno-regulatory epitopes show a long-term treatment effect in cat allergic subjects journal April 2015
Cat allergen-induced blood basophil reactivity in vitro predicts acute human nasal allergen challenge responses in vivo: Clinical Mechanisms in Allergic Disease journal March 2011
Functional rather than immunoreactive levels of IgG4 correlate closely with clinical response to grass pollen immunotherapy: Functional IgG4 correlates with clinical efficacy of allergen specific immunotherapy journal November 2011
Prophylactic Inoculation against Hay Fever journal January 1953
Epitope-specific T cell tolerance to phospholipase A2 in bee venom immunotherapy and recovery by IL-2 and IL-15 in vitro. journal October 1996
IgG-mediated down-regulation of IgE bound to mast cells: a potential novel mechanism of allergen-specific desensitization text January 2014

Cited By (12)

Next-Generation of Allergen-Specific Immunotherapies: Molecular Approaches journal June 2018
IgE Antibodies: From Structure to Function and Clinical Translation journal February 2019
An Engineered Hybrid Protein from Dermatophagoides pteronyssinus Allergens Shows Hypoallergenicity journal June 2019
Resistance of parvalbumin to gastrointestinal digestion is required for profound and long‐lasting prophylactic oral tolerance journal May 2019
Keep the cat, change the care pathway: A transformational approach to managing Fel d 1, the major cat allergen journal October 2019
Recent developments and highlights in food allergy journal June 2019
High-affinity allergen-specific human antibodies cloned from single IgE B cell transcriptomes journal December 2018
Chronic allergen exposure drives accumulation of long-lived IgE plasma cells in the bone marrow, giving rise to serological memory journal January 2020
The use of biologics for immune modulation in allergic disease journal March 2019
Allergen-Specific Antibodies Regulate Secondary Allergen-Specific Immune Responses journal January 2019
A Human IgE Antibody Binding Site on Der p 2 for the Design of a Recombinant Allergen for Immunotherapy journal September 2019
The use of biologics for immune modulation in allergic disease text January 2019

Figures / Tables (6)

Fig. 1(p. 3)figure Fig. 1
Figure-2(p. 4)figure Figure-2
Fig. 3(p. 6)figure Fig. 3
Fig. 4(p. 7)figure Fig. 4
Fig. 5(p. 8)figure Fig. 5
Table 1(p. 9)table Table 1

Similar Records

Immunotherapy-induced neutralizing antibodies disrupt allergen binding and sustain allergen tolerance in peanut allergy
Journal Article · Mon Jan 16 19:00:00 EST 2023 · Journal of Clinical Investigation · OSTI ID:2423466
Human Monoclonal IgE Antibodies—a Major Milestone in Allergy
Journal Article · Thu Dec 01 19:00:00 EST 2022 · Current Allergy and Asthma Reports · OSTI ID:2423460

Related Subjects