Allergenicity, immunogenicity and dose-relationship of three intact allergen vaccines and four allergoid vaccines for subcutaneous grass pollen immunotherapy

Henmar, H.; Lund, G.; Lund, L.; Petersen, Anita; Würtzen, Peter Adler

doi:10.1111/j.1365-2249.2008.03710.x

Cited by 46 publications

(40 citation statements)

References 30 publications

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“…To investigate the effect of basophil desensitization on the basophil phenotype at single cell level, we measured expression of basophil cell surface markers CD63 and CD203c. The expression of these markers on blood basophils is known to be increased following IgE-dependent activation and is widely used for measuring basophil activation in allergy diagnostics [23,26,27,28] as well as for measuring allergenicity [29,30]. …”

Section: Discussionmentioning

confidence: 99%

Effect on Cell Surface Markers following Allergen-Induced Desensitization of Human Whole-Blood Basophils

Lund

Jacobi²,

Skov³

et al. 2010

Int Arch Allergy Immunol

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Background: Allergen-specific immunotherapy (SIT) leads to reduced symptoms upon allergen exposure through as yet unresolved mechanisms. Desensitization of basophils to specific allergens during the updosing phase of injection immunotherapy may contribute to the clinical effect of SIT. Here we report a protocol for efficient in vitro allergen-mediated desensitization of basophils in whole blood and the effect of desensitization on the expression of basophil activation markers (CD203c and CD63) as well as histamine release in response to allergen challenge. Methods: Whole blood from grass pollen-allergic subjects was incubated with Phleum pratense extract by stepwise increase of the allergen concentration in the culture from well below to well above the allergen threshold concentration for activation of basophils. Desensitization was determined by measuring the expression of the basophil activation markers CD63 and CD203c by FACS following challenge with high allergen concentrations. Results: The basophil desensitization protocol reported here affected both the expression of the cell-surface markers and the levels of histamine release. Following the stepwise desensitization procedure the whole-blood basophils were not activated when challenged with more than 10-fold increased allergen concentration. Conclusion: We have established a protocol for basophil desensitization. By mimicking the updosing phase of immunotherapy we raised the allergen threshold for basophil activation and obtained efficient desensitization for all donors. We showed that conditions leading to desensitization affect histamine release and expression of different basophil markers alike.

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Section: Discussionmentioning

confidence: 99%

Effect on Cell Surface Markers following Allergen-Induced Desensitization of Human Whole-Blood Basophils

Lund

Jacobi²,

Skov³

et al. 2010

Int Arch Allergy Immunol

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“…One concern is that the low allergenicity of allergoids in comparison to standard extracts may actually be associated with reduced immunogenicity [16]. Nonetheless, this remains a promising alternative approach to traditional SCIT, and future studies should be encouraged.…”

Section: Allergoidsmentioning

confidence: 99%

“…Glutaraldehyde and formaldehyde have been used to modify allergens and produce allergoids, which reduce IgE epitopes (allergenicity) while preserving T-cell epitopes (immunogenicity) [16]. Allergoids are commonly used in European SCIT, but there are no current FDA-approved products in the United States.…”

Section: Allergoidsmentioning

confidence: 99%

Novel Approaches of Immunotherapy

Stokes

Casale

2013

Curr Treat Options Allergy

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Opinion statementAllergic diseases affect millions of adults and children in the United States. Allergen immunotherapy has been a treatment option for diseases such as allergic rhinitis, allergic asthma, and venom allergy for the last 100 years. In the last 25 years, alternative approaches to traditional subcutaneous immunotherapy have been developed. The purpose of these new therapies is two-fold: to improve safety and to improve the efficacy of allergen immunotherapy. Aluminum hydroxide has been used as an adjuvant to standard immunotherapy, but due to concerns about side effects, its use has been decreasing. The modification of allergens into allergoids has been an effective therapy in Europe, but at this time no preparations are available for use in the United States. Toll-like receptors have demonstrated mixed results with early trials in the United States, showing promise with the use of a TLR4 agonist, while a TLR9 agonist had disappointing results. Early studies with the use of virus-like particles with and without allergens have shown additional promise, and further trials are currently underway. These novel approaches may improve the immunologic response and often the clinical outcomes for the management of allergic diseases.

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“…Pre-generated Bet v 1-or Phl p 5-specific T cell lines [40,41] were thawed, washed and cultured in RPMI with 5% human AB-serum (Lonza; cat. no 14-490E).…”

Section: T Cell Line Generationmentioning

confidence: 99%

Direct contact between dendritic cells and bronchial epithelial cells inhibits T cell recall responses towards mite and pollen allergen extracts in vitro

Wagtmann

Hansen

Würtzen

2015

Clinical and Experimental Immunology

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SummaryAirway epithelial cells (AECs) form a polarized barrier along the respiratory tract. They are the first point of contact with airborne antigens and are able to instruct resident immune cells to mount appropriate immune responses by either soluble or contact-dependent mechanisms. We hypothesize that a healthy, polarized epithelial cell layer inhibits inflammatory responses towards allergens to uphold homeostasis. Using an in-vitro co-culture model of the airway epithelium, where a polarized cell layer of bronchial epithelial cells can interact with dendritic cells (DCs), we have investigated recall T cell responses in allergic patients sensitized to house dust mite, grass and birch pollen. Using allergen extract-loaded DCs to stimulate autologous allergen-specific T cell lines, we show that AEC-imprinted DCs inhibit T cell proliferation significantly of Bet v 1-specific T cell lines as well as decrease interleukin (IL)-5 and IL-13 production, whereas inhibition of Phl p 5-specific T cells varied between different donors. Stimulating autologous CD4 1 T cells from allergic patients with AEC-imprinted DCs also inhibited proliferation significantly and decreased production of both T helper type 1 (Th1) and Th2 cytokines upon rechallenge. The inhibitory effects of AECs' contact with DCs were absent when allergen extract-loaded DCs had been exposed only to AECs supernatants, but present after direct contact with AECs. We conclude that direct contact between DCs and AECs inhibits T cell recall responses towards birch, grass and house dust mite allergens in vitro, suggesting that AECs-DC contact in vivo constitute a key element in mucosal homeostasis in relation to allergic sensitisation.

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Allergenicity, immunogenicity and dose-relationship of three intact allergen vaccines and four allergoid vaccines for subcutaneous grass pollen immunotherapy

Cited by 46 publications

References 30 publications

Effect on Cell Surface Markers following Allergen-Induced Desensitization of Human Whole-Blood Basophils

Effect on Cell Surface Markers following Allergen-Induced Desensitization of Human Whole-Blood Basophils

Novel Approaches of Immunotherapy

Direct contact between dendritic cells and bronchial epithelial cells inhibits T cell recall responses towards mite and pollen allergen extracts in vitro

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