Endotoxin content of standardized allergen vaccines

Trivedi, B.; Valerio, C.; Slater, Jay E.

doi:10.1067/mai.2003.1338

Cited by 92 publications

(86 citation statements)

References 22 publications

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“…However, these findings are controversial (8)(9)(10), and there is a lack of consensus regarding the mechanisms by which alum induces systemic Th2 immunity (11,12). Although many naturally occurring allergens and allergenic extracts are used to study Th2-driven responses, these preparations often are contaminated with multiple MAMPs (13,14), thereby confounding the interpretation of the specific roles of different MAMPs in the generation of Th2 immunity in these contexts. The agonists that activate Nod1 and Nod2 receptors are chemically defined and have been shown to induce Th2 immunity (15,16), although the mechanisms underlying this response remain ill-defined.…”

mentioning

confidence: 99%

Nucleotide oligomerization domain-containing proteins instruct T cell helper type 2 immunity through stromal activation

Magalhães¹,

Rubino

Travassos³

et al. 2011

Proc. Natl. Acad. Sci. U.S.A.

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Although a number of studies have examined the development of T-helper cell type 2 (Th2) immunity in different settings, the mechanisms underlying the initiation of this arm of adaptive immunity are not well understood. We exploited the fact that immunization with antigen plus either nucleotide-binding oligomerization domain-containing proteins 1 (Nod1) or 2 (Nod2) agonists drives Th2 induction to understand how these pattern-recognition receptors mediate the development of systemic Th2 immune responses. Here, we show in bone-marrow chimeric mice that Nod1 and Nod2 expression within the stromal compartment is necessary for priming of effector CD4 + Th2 responses and specific IgG1 antibodies. In contrast, sensing of these ligands by dendritic cells was not sufficient to induce Th2 immunity, although these cells contribute to the response. Moreover, we determined that CD11c + cells were the critical antigen-presenting cells, whereas basophils and B cells did not affect the capacity of Nod ligands to induce CD4 + Th2 effector function. Finally, we found that full Th2 induction upon Nod1 and Nod2 activation was dependent on both thymic stromal lymphopoietin production by the stromal cells and the up-regulation of the costimulatory molecule, OX40 ligand, on dendritic cells. This study provides in vivo evidence of how systemic Th2 immunity is induced in the context of Nod stimulation. Such understanding will influence the rational design of therapeutics that could reprogram the immune system during an active Th1–mediated disease, such as Crohn's disease.

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mentioning

confidence: 99%

Nucleotide oligomerization domain-containing proteins instruct T cell helper type 2 immunity through stromal activation

Magalhães¹,

Rubino

Travassos³

et al. 2011

Proc. Natl. Acad. Sci. U.S.A.

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“…We believe that the majority of disadvantages that limit the broad applicability of SIT are related to the poor quality of allergen extracts [25][26][27][28][29][30][31][32]. SIT seems to be less effective for certain clinical manifestations of allergy such as asthma, food allergy and atopic dermatitis and for certain allergen sources such as house dust mites, moulds, cat, dog and food allergens [12].…”

Section: Factors Limiting the Broad Application Of Allergen-specific mentioning

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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“…12,13 In addition, in the last few years, second generation treatments based on recombinant allergens (in a natural or hypoallergenic conformation), fusions proteins, mix of peptides, plasmid DNA have raised considerable interest, even if none of those molecular allergens have reached commercialization. [14][15][16] However, in contrast to natural extracts which often possess an intrinsic adjuvant activity (e.g., Th2-inducing activity ascribed to the Der p 1 mite allergen, endotoxin, phytoprostanes), 17,18 purified allergens provided under such a well defined molecular form are usually poorly immunogenic. Thus, such second generation vaccines will also require novel immunopotentiators and vector systems (collectively referred to as adjuvants in the present review).…”

Section: Adjuvants For Allergy Vaccinesmentioning

confidence: 99%

Adjuvants for allergy vaccines

Moingeon

2012

Human Vaccines & Immunotherapeutics

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Endotoxin content of standardized allergen vaccines

Cited by 92 publications

References 22 publications

Nucleotide oligomerization domain-containing proteins instruct T cell helper type 2 immunity through stromal activation

Nucleotide oligomerization domain-containing proteins instruct T cell helper type 2 immunity through stromal activation

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

Adjuvants for allergy vaccines

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