Der p 1 peptide on virus-like particles is safe and highly immunogenic in healthy adults

Kündig, Thomas M.; Senti, Gabriela; Schnetzler, Gabriel; Wolf, Charles; Vavricka, Bettina M. Prinz; Fulurija, Alma; Hennecke, Frank; Sladko, Katja; Jennings, Gary T.; Bachmann, Martin F.

doi:10.1016/j.jaci.2006.01.040

Cited by 181 publications

(144 citation statements)

References 38 publications

Supporting

Mentioning

136

Contrasting

Unclassified

Order By: Relevance

“…The use of these hypoallergenic recombinant vaccines holds the promise of inducing fewer side effects during therapy. Der p1 peptides have also been delivered on virus‐like particles, inducing IgG responses within 4 weeks after a single injection in healthy subjects 29. Both of these approaches involve the use of recombinant hypoallergenic proteins or peptides, while we use purified natural proteins, with high purity and pharmacologically well defined, but retaining the activity to crosslink IgE.…”

Section: Discussionmentioning

confidence: 99%

Subcutaneous immunotherapy with purified Der p1 and 2 suppresses type 2 immunity in a murine asthma model

Hesse

Ieperen

Habraken

et al. 2018

Allergy

View full text Add to dashboard Cite

BackgroundAllergen‐specific immunotherapy can induce long‐term suppression of allergic symptoms, reduce medication use, and prevent exacerbations of allergic rhinitis and asthma. Current treatment is based on crude allergen extracts, which contain immunostimulatory components such as β‐glucans, chitins, and endotoxin. Use of purified or recombinant allergens might therefore increase efficacy of treatment.AimsHere, we test application of purified natural group 1 and 2 allergens from Dermatophagoides pteronyssinus (Der p) for subcutaneous immunotherapy (SCIT) treatment in a house dust mite (HDM)‐driven mouse model of allergic asthma.Materials and methods HDM‐sensitized mice received SCIT with crude HDM extract, a mixture of purified Der p1 and 2 (DerP1/2), or placebo. Upon challenges, we measured specific immunoglobulin responses, allergen‐induced ear swelling response (ESR), airway hyperresponsiveness (AHR), and inflammation in bronchoalveolar lavage fluid (BAL) and lung tissue.Results ESR measurement shows suppression of early allergic response in HDM‐SCIT– and DerP1/2‐SCIT–treated mice. Both HDM‐SCIT and DerP1/2‐SCIT are able to suppress AHR and eosinophilic inflammation. In contrast, only DerP1/2‐SCIT is able to significantly suppress type 2 cytokines in lung tissue and BAL fluid. Moreover, DerP1/2‐SCIT treatment is uniquely able suppress CCL20 and showed a trend toward suppression of IL‐33, CCL17 and eotaxin levels in lung tissue.DiscussionTaken together, these data show that purified DerP1/2‐SCIT is able to not only suppress AHR and inflammation, but also has superior activity toward suppression of Th2 cells and HDM‐induced activation of lung structural cells including airway epithelium.ConclusionsWe postulate that treatment with purified natural major allergens derived from HDM will likely increase clinical efficacy of SCIT.

show abstract

Section: Discussionmentioning

confidence: 99%

Subcutaneous immunotherapy with purified Der p1 and 2 suppresses type 2 immunity in a murine asthma model

Hesse

Ieperen

Habraken

et al. 2018

Allergy

View full text Add to dashboard Cite

show abstract

“…In a similar approach, vaccination of healthy adults with a peptide antigen covalently coupled to highly repetitive virus-like bacteriophage particles induced high IgG antibody titres against the allergen [121].…”

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

View full text Add to dashboard Cite

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.

show abstract

“…Immunization of healthy subjects by subcutaneous administration of the conjugate induced Der p 1-specific IgG antibodies [65]. It was also shown that the coupling to virus-like particles reduced the allergenic activity of the major cat allergen Fel d 1 [66].…”

Section: Cpg-conjugated and Other Coupled Allergensmentioning

confidence: 95%

“…Allergens that are chemically coupled to virus-like particles [65,66] Genetic vaccines DNA vaccines -Vaccination with allergen-encoding DNA [88][89][90][91][92][93] RNA vaccines -Vaccination with allergen-encoding RNA [94] B. Alternative routes Sublingual -Sublingual administration of allergen-containing drops or tablets [17,24,[74][75][76][77][78][79] Oral -Oral administration of allergens (i.e.…”

Section: Coupled Allergensmentioning

confidence: 99%

Allergen‐specific immunotherapy: from therapeutic vaccines to prophylactic approaches

Valenta

Campana

Marth

et al. 2012

Journal of Internal Medicine

101

View full text Add to dashboard Cite

Immunoglobulin E-mediated allergies affect more than 25% of the population. Allergen exposure induces a variety of symptoms in allergic patients, which include rhinitis, conjunctivitis, asthma, dermatitis, food allergy and life-threatening systemic anaphylaxis. At present, allergen-specific immunotherapy (SIT), which is based on the administration of the disease-causing allergens, is the only diseasemodifying treatment for allergy. Current therapeutic allergy vaccines are still prepared from relatively poorly defined allergen extracts. However, with the availability of the structures of the most common allergen molecules, it has become possible to produce well-defined recombinant and synthetic allergy vaccines that allow specific targeting of the mechanisms of allergic disease. Here we provide a summary of the development and mechanisms of SIT, and then review new forms of therapeutic vaccines that are based on recombinant and synthetic molecules. Finally, we discuss possible allergen-specific strategies for prevention of allergic disease.

show abstract

Der p 1 peptide on virus-like particles is safe and highly immunogenic in healthy adults

Cited by 181 publications

References 38 publications

Subcutaneous immunotherapy with purified Der p1 and 2 suppresses type 2 immunity in a murine asthma model

Subcutaneous immunotherapy with purified Der p1 and 2 suppresses type 2 immunity in a murine asthma model

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

Allergen‐specific immunotherapy: from therapeutic vaccines to prophylactic approaches

Contact Info

Product

Resources

About