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Allergen immunotherapy (IT) is a proven approach for treating allergic rhinitis and allergic asthma that has been practiced since 1911 and has undergone significant development in the past two decades. As currently practiced, IT involves subcutaneous or sublingual administration of allergens, both methods of which have been extensively investigated. In addition to allergen IT, a number of additional nonspecific IT approaches are being used or are in phase II/phase III clinical trials, which may be available in clinics within the next one to three years. Such therapies include anti-IgE antibodies and the soluble IL-4 receptor. Other experimental IT approaches are at the preclinical research stage and may proceed to clinical trials and the clinic within the next five to ten years. This review discusses the pros and cons of recent developments in both currently practiced and experimental IT approaches., (Copyright 2010 Elsevier Ltd. All rights reserved.)

Among pollen allergens, grass pollen allergens are some of the most frequent contributors to allergic symptoms. Substantial progress has been made since the 1960s in the identification and characterization of the grass allergens. Members of this group belong to the Poaceae family, and have been classified into 13 distinct groups based on their structure, and their biological and immunologic properties. The major contributors to allergy and, hence, most studied among the grass allergens, are those belonging to groups 1 and 5. This review is focused on the structure and immunobiology of the grass allergens and highlights how recent advances in the field have contributed to superior diagnosis and immunotherapy for allergy to grass pollens.

Background: Plasmids encoding cytokines such as IFN-gamma and IL-12 are potential genetic adjuvants that might increase the effectiveness of allergen vaccines., Objective: The role of plasmids expressing the cytokines IFN-gamma (pIFN-gamma) and/or IL-12 (pIL-12) as adjuvants in modulating allergic immune responses, inflammation, and asthma was investigated in a murine model of Kentucky blue grass (KBG) allergy., Methods: Groups of naive B6D2F1 mice were vaccinated subcutaneously with KBG allergens and administered intramuscularly with pIFN-gamma, pIL-12, pIFN-gamma plus pIL-12, or a vector control. Mice were then sensitized with KBG allergens in alum (intraperitoneally) and later challenged intranasally. Mice were examined for modulation of specific immunity, prevention of the development of airway hyperresponsiveness, and inflammation., Results: Mice vaccinated with cytokine plasmid adjuvants had relatively lower levels of total serum IgE and higher levels of grass allergen-specific IgG2a in comparison with control mice. The lowest IgE and highest IgG2a levels were found in mice vaccinated with the combination of pIFN-gamma and pIL-12 as an adjuvant. The vaccination of mice with both pIFN-gamma and pIL-12 as an adjuvant induced the highest level of T(H)1 cytokines, IFN-gamma, and IL-2 in comparison with mice given either of the plasmids alone. The most profound decrease in airway hyperresponsiveness and pulmonary inflammation was observed in mice receiving both pIFN-gamma and pIL-12 as an adjuvant., Conclusion: These results demonstrate that pIFN-gamma and pIL-12 together provide an effective adjuvant to parenteral grass allergen vaccines and show that this adjuvant can significantly enhance the effectiveness of allergen immunotherapy in human beings.

To evaluate the use of recombinant allergens for the diagnosis of grass pollen allergies, we examined the levels of IgE antibodies specific for grass pollen as by immunoassays. SDS-PAGE analysis of two batches of Kentucky bluegrass pollen extracts demonstrated that there was considerable variability in allergen content of extracts, which in turn affected quantitation of specific IgE antibodies by different immunoassay procedures. Furthermore, the levels of IgE antibodies in human sera specific for a recombinant grass pollen allergen, rKBG8.3, were examined by enzyme immunoassay. The results demonstrated that quantitation of IgE antibodies specific for even one single allergen may be used to discriminate sera of allergic individuals with respect to IgE specific for grass pollen in general. A positive correlation, r = .82, was found for IgE binding of the recombinant allergen and the crude extracts of grass pollens. It is concluded from these results that a single recombinant allergen or a combination of a few major recombinant allergens can substitute the crude extract for in vitro as well as in vivo diagnostic purposes.

The allergenic and antigenic cross-reactivities between a major recombinant Poa pratensis (Poa p) IX allergen, rKBG8.3, and its corresponding proteins of different grass pollens were examined. Immunoblotting of the proteins of thirteen different grass pollens using anti-rKBG8.3 antibodies indicated that Poa p IX-like proteins are present in ten other grass pollens, albeit in variable amounts and polymorphic forms. These proteins ranged in size from 20 to 88 kDa in different grass pollens. The percent relative binding determined for each grass pollen extract using allergic human sera showed a significant correlation (r = 0.891) with that of anti-rKBG8.3 antiserum. Moreover, there was a strong association (r = 0.901) between the Kentucky bluegrass extract and rKBG8.3 with respect to their inhibition of the binding of human IgE antibodies to allergens in grass pollen extracts. Taken together, these results suggest that the allergenic and antigenic epitopes of the Poa p IX-related proteins in some but not all grass pollens are similar in structure and specificities. It is concluded that the group IX allergens constitute a major family of homologous proteins in several grass pollens.