Passive immunization with allergen-specific IgG antibodies for treatment and prevention of allergy

Flicker, Sabine; Linhart, Birgit; Wild, C.; Wiedermann, Ursula; Valenta, Rudolf

doi:10.1016/j.imbio.2012.10.008

Cited by 43 publications

(38 citation statements)

References 32 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Whether BP-specific IgG2a antibodies have a functional role or whether they are more an epi-phenomenon of another pathway still has to be explored. A possible mechanism could be via competition for IgE-mediated basophil release, as recently described in BP-sensitised mice, in which treatment with rabbit anti-Bet v1 IgG inhibited IgE-mediated basophil degranulation [17]. In support of a functional role for BP-specific IgG2a, intratracheal instillation of OVA-specific IgG2a or IgG1 in mice with OVA-induced allergic asthma was sufficient to suppress AHR after OVA aerosol challenge [18].…”

Section: Discussionmentioning

confidence: 95%

Birch Pollen Immunotherapy in Mice: Inhibition of Th2 Inflammation Is Not Sufficient to Decrease Airway Hyper-Reactivity

Rijt¹,

Gouveia²,

Logiantara³

et al. 2014

Int Arch Allergy Immunol

View full text Add to dashboard Cite

Background: Suppression of Th2 cytokine production by allergen-specific Th2 cells is considered to be critical for the suppression of allergic symptoms by subcutaneous immunotherapy. The aim of this study was to develop a mouse model for birch pollen (BP) immunotherapy to elucidate the underlying mechanisms that contribute to the improvement of clinical symptoms. Methods: Mice with BP-induced allergic airway inflammation received weekly subcutaneous immunotherapy (SCIT) injections with BP extract (BPE) adsorbed to alum. The effect of an increasing dose of BPE adsorbed to a fixed concentration of alum on the suppression of airway inflammation and airway hyper-responsiveness (AHR) was determined. After 2, 4, 6 or 8 immunotherapy injections, the mice were rechallenged with the same allergen and all hallmarks of allergic asthma were evaluated. Results: Suppression of the immunological parameters by immunotherapy was dependent on the BPE dose. Two injections were sufficient to suppress IL-4, IL-5, IL-13, IL-10 and IFN-G production, eosinophil recruitment and peribronchial inflammatory infiltrates. BP-specific immunoglobulins were upregulated, but this was not sufficient to reduce AHR. Eight injections were needed to suppress AHR. The gradual reduction in AHR was inversely associated with the increase of BP IgG2a. Conclusions: BP SCIT induces an early suppression of Th2-mediated eosinophilic airway inflammation, but AHR is only effectively reduced after continued SCIT conceivably by allowing IgG2a antibody titres to build up. i 2014 S. Karger AG, Basel

show abstract

Section: Discussionmentioning

confidence: 95%

Birch Pollen Immunotherapy in Mice: Inhibition of Th2 Inflammation Is Not Sufficient to Decrease Airway Hyper-Reactivity

Rijt¹,

Gouveia²,

Logiantara³

et al. 2014

Int Arch Allergy Immunol

View full text Add to dashboard Cite

show abstract

“…Further studies should be conducted using absorption methods or purification of specific IgG1 or IgG4 fractions from patients that are single positive for each IgG subclass to evaluate separately the role of each subclass of specific IgG fraction. This blocking role of allergen-specific IgG antibodies has been recently investigated in mouse models through passive immunization with specific IgG antibodies for prevention and treatment of allergy to major birch and grass pollen allergens [39]. The authors showed that mice treated with anti-Phl p 1 IgG after sensitization with rPhl p 1 allergen had reduced Phl p 1-specific IgE levels in all time points tested.…”

Section: Discussionmentioning

confidence: 99%

Allergen-Specific IgG Antibodies Purified from Mite-Allergic Patients Sera Block the IgE Recognition ofDermatophagoides pteronyssinusAntigens: AnIn VitroStudy

Siman

Aquino

Ynoue

et al. 2013

Clinical and Developmental Immunology

View full text Add to dashboard Cite

One of the purposes of specific immunotherapy (SIT) is to modulate humoral immune response against allergens with significant increases in allergen-specific IgG levels, commonly associated with blocking activity. The present study investigated in vitro blocking activity of allergen-specific IgG antibodies on IgE reactivity to Dermatophagoides pteronyssinus (Dpt) in sera from atopic patients. Dpt-specific IgG antibodies were purified by ammonium sulfate precipitation followed by protein-G affinity chromatography. Purity was checked by SDS-PAGE and immunoreactivity by slot-blot and immunoblot assays. The blocking activity was evaluated by inhibition ELISA. The electrophoretic profile of the ammonium sulfate precipitated fraction showed strongly stained bands in ligand fraction after chromatography, compatible with molecular weight of human whole IgG molecule. The purity degree was confirmed by detecting strong immunoreactivity to IgG, negligible to IgA, and no reactivity to IgE and IgM. Dpt-specific IgG fraction was capable of significantly reducing levels of IgE anti-Dpt, resulting in 35%–51% inhibition of IgE reactivity to Dpt in atopic patients sera. This study showed that allergen-specific IgG antibodies purified from mite-allergic patients sera block the IgE recognition of Dermatophagoides pteronyssinus antigens. This approach reinforces that intermittent measurement of serum allergen-specific IgG antibodies will be an important objective laboratorial parameter that will help specialists to follow their patients under SIT.

show abstract

“…ELISA plates were coated with a mix of Phl p 1, Phl p 2, Phl p 5, and Phl p 6 (5 mg of each allergen/ml bicarbonate buffer); sera were diluted 1:10 for IgE detection and 1:50,000 for rabbit IgG detection. The degranulation experiment of rat basophil leukemia cells was performed as previously described (28). Cells were cultivated overnight in 96-well plates, washed twice, and incubated with mouse serum diluted 1:10 in Tyrode's buffer, together with a mix of Phl p 1, Phl p 2, Phl p 5, and Phl p 6 (0.1 mg/ml of each allergen) for 2 h, and b-hexosaminidase release was measured in supernatants.…”

Section: Development Of a Murine Model For The Treatment Of Grass Polmentioning

confidence: 99%

Molecular Evolution of Hypoallergenic Hybrid Proteins for Vaccination against Grass Pollen Allergy

Linhart

Focke‐Tejkl

Weber

et al. 2015

The Journal of Immunology

Self Cite

View full text Add to dashboard Cite

More than 10% of the population in Europe and North America suffer from IgE-associated allergy to grass pollen. In this article, we describe the development of a vaccine for grass pollen allergen-specific immunotherapy based on two recombinant hypoallergenic mosaic molecules, designated P and Q, which were constructed out of elements derived from the four major timothy grass pollen allergens: Phl p 1, Phl p 2, Phl p 5, and Phl p 6. Seventeen recombinant mosaic molecules were expressed and purified in Escherichia coli using synthetic genes, characterized regarding biochemical properties, structural fold, and IgE reactivity. We found that depending on the arrangement of allergen fragments, mosaic molecules with strongly varying IgE reactivity were obtained. Based on an extensive screening with sera and basophils from allergic patients, two hypoallergenic mosaic molecules, P and Q, incorporating the primary sequence elements of the four grass pollen allergens were identified. As shown by lymphoproliferation experiments, they contained allergen-specific T cell epitopes required for tolerance induction, and upon immunization of animals induced higher allergen-specific IgG Abs than the wild-type allergens and a registered monophosphoryl lipid A–adjuvanted vaccine based on natural grass pollen allergen extract. Moreover, IgG Abs induced by immunization with P and Q inhibited the binding of patients’ IgE to natural allergens from five grasses better than IgG induced with the wild-type allergens or an extract-based vaccine. Our results suggest that vaccines based on the hypoallergenic grass pollen mosaics can be used for immunotherapy of grass pollen allergy.

show abstract

Passive immunization with allergen-specific IgG antibodies for treatment and prevention of allergy

Cited by 43 publications

References 32 publications

Birch Pollen Immunotherapy in Mice: Inhibition of Th2 Inflammation Is Not Sufficient to Decrease Airway Hyper-Reactivity

Birch Pollen Immunotherapy in Mice: Inhibition of Th2 Inflammation Is Not Sufficient to Decrease Airway Hyper-Reactivity

Allergen-Specific IgG Antibodies Purified from Mite-Allergic Patients Sera Block the IgE Recognition ofDermatophagoides pteronyssinusAntigens: AnIn VitroStudy

Molecular Evolution of Hypoallergenic Hybrid Proteins for Vaccination against Grass Pollen Allergy

Contact Info

Product

Resources

About