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PubMedDate not supplied

Allergen immunotherapy: guidelines, update, and recommendations of the World Health Organization.

Allergen immunotherapy (AIT) is the administration of increasing doses of an allergen vaccine to an allergic subject in order to reach a dose effective to improve symptoms associated with subsequent exposure to the causative allergen. This form of therapy is effective in the treatment of allergic rhinitis/conjunctivitis, allergic reactions to stinging insects, and allergic asthma. It is the only therapeutic modality that can affect the natural course of allergic diseases, and may prevent the development of asthma in patients with allergic rhinitis. AIT is indicated for patients with demonstrated specific IgE antibodies against clinically relevant allergens. The mixture of allergens to be utilized is based on the patient's history and skin and laboratory tests. The major risk of AIT is anaphylaxis. Such therapy is continued for three to five years, but the decision to discontinue it should be individualized. Interpretation of the history, physical findings, and skin and laboratory tests, the prescription and administration of allergen immunotherapy, its integration into the patient's treatment plan, and the decision to discontinue it require qualifying experience provided by specialist training in allergy and immunology.

Desensitization, Immunologic↗
PubMed1964

THE IMMUNOLOGY OF ALLERGY.

The symptomatic treatment of allergic disorders is of major importance but more profound benefits can be obtained by understanding and applying the immunologic principles involved in allergic diseases.Immediate hypersensitivity diseases such as hay fever and asthma are the result of a combination of allergic antibody and allergens. The chemical mediators liberated by this union produce tissue effects resulting in the manifestation of allergic symptoms. Specific hyposensitization treatment alters the allergic immunologic reaction pattern.

Allergens↗
PubMed2004

Selective immune redirection in humans with ragweed allergy by injecting Amb a 1 linked to immunostimulatory DNA.

BACKGROUND: In animal models administration of immunostimulatory DNA sequences preferentially elicits T(H)1-dominated (type 1-dominated) immunity and can inhibit developing or ongoing T(H)2 (type 2) responses. OBJECTIVE: Our objective was to investigate this phenomenon in humans. METHODS: In a randomized, third party-blinded, placebo-controlled, proof-of-concept study conducted entirely in the winter in 19 adults with ragweed allergy, we administered 6 subcutaneous injections of purified Amb a 1 linked to the 22-base-long immunostimulatory phosphorothioate oligodeoxyribonucleotide 1018 (Amb a 1-immunostimulatory DNA sequence conjugate [AIC]). Before the course of AIC or placebo injections and 2 and 16 weeks afterward, we measured recall responses to ragweed, streptokinase, and PHA in short-term primary culture of fresh PBMCs after restimulation with antigen. We quantified regulatory cytokine and chemokine responses characteristic of T(H)2 immunity (IL-5, IL-13, CCL17 [TARC], and CCL22 [MDC]), and T(H)1 immunity (IFN-gamma, CXCL9 [Mig], and CXCL10 [IP-10]), as well as IL-10, a cytokine sometimes linked to regulatory T-cell populations. RESULTS: We demonstrated for the first time that human systemic in vivo ragweed-specific T(H)2 responses were selectively redirected toward T(H)1 responses, with significant increases in IFN-gamma, CXCL9, and CXCL10 and significant decreases in IL-5, CCL17, and CCL22 found at 2 and 16 weeks after the sixth injection. Cytokine and chemokine responses to the unrelated bacterial antigen streptokinase and the global capacity to mount immune responses on polyclonal activation with PHA did not change. No clinically significant systemic or local allergic reactions were associated with AIC or placebo injections. CONCLUSIONS: AIC, injected in concentrations that were approximately 40-fold lower than those used in most murine studies published to date, led to a prolonged shift from T(H)2 immunity toward T(H)1 immunity and appeared to be safe. This novel approach has the potential for immune redirection in human immediate hypersensitivity diseases.

Adjuvants, Immunologic↗
PubMed2003

Negative venom skin test results in patients with histories of systemic reaction to a sting.

For more than 20 years venom immunotherapy has been the preferred treatment for Hymenoptera allergy and venom skin testing the preferred diagnostic test. Most allergists consider venom skin tests to be highly accurate and interpret a negative venom skin test result to indicate the absence of insect allergy. Furthermore, current practice guidelines do not adequately address the question of how best to manage the patient with a convincing history of insect allergy but negative skin test results. Recent case reports and published studies have forced us to reexamine this important management issue and to consider what role in vitro venom testing might have in the management of insect allergy. We reviewed the current status of what is known about the management of individuals with a history of insect allergy but negative venom skin test results and suggested modifications of current working guidelines.

Anaphylaxis↗
PubMedDate not supplied

Efficacy and tolerability of short-term specific immunotherapy with pollen allergoids adjuvanted by monophosphoryl lipid A (MPL) for children and adolescents.

BACKGROUND: Specific immunotherapy (SIT) with pollen allergoids formulated with the Th1-inducing adjuvant 3-deacylated monophosphoryl lipid A (MPL adjuvant, Corixa) has shown good efficacy and tolerability in the treatment of pollen allergies in adults. The aim of this study was to evaluate this treatment in children and adolescents aged 6-17 years old who were sensitive to grass/rye or tree pollens. METHODS: An open, multicenter study was performed using 90 children and adolescents. The patients received four subcutaneous injections of grass/rye (n = 64) or tree pollen allergoids (n = 26) adsorbed to L-tyrosine and containing MPL adjuvant. Efficacy was measured by symptom and medication scoring, skin prick test reactivity and IgG/IgE antibody responses. Tolerability was monitored by recording adverse events. RESULTS: Both grass/rye and tree pollen treatment groups showed significant reductions in symptom scores and anti-allergic medication use compared with the previous pollen seasons (p < 0.01 in all cases). After therapy, skin prick test reactivity was significantly reduced in both groups and pollen-specific IgG was significantly increased in both groups whereas little change was apparent in pollen-specific IgE. Overall tolerability was similar to results obtained in previous studies in adults. CONCLUSION: Short-term SIT using four injections of grass/rye or tree pollen allergoids adsorbed to L-tyrosine and with MPL adjuvant was shown to be effective with good tolerability. The treatment compared favorably with previous studies in adults.

Adjuvants, Immunologic↗
PubMed2004

Adjuvants for allergen immunotherapy: experimental results and clinical perspectives.

PURPOSE OF REVIEW: Inclusion of adjuvants in immunotherapy vaccines are important to enhance immune responses to allergens. This article will cover the recent advances in adjuvant formulations described in published articles primarily over the past 2 years. RECENT FINDINGS: Traditionally, allergen immunotherapy preparations utilize aluminium hydroxide as an adjuvant. These have generally proved efficacious and have a good safety profile. However, recent advances in the understanding of immunological mechanisms underlying immunotherapy and in the design of new adjuvants may allow a more rational approach to adjuvant use. One approach is to use adjuvants such as immunostimulatory sequences or monophosphoryl lipid A, which can deviate allergy-associated Th2 immune responses towards a Th1 phenotype. Both of these adjuvants have been used in pilot controlled clinical trials which have demonstrated clinical efficacy and the induction of protective IgG antibodies. Other approaches to improve immunotherapy vaccines include microencapsulation of allergen to allow delivery of the allergen directly to the gut in order to induce immunological tolerance and vaccination with heat-killed mycobacteria. SUMMARY: There is great interest in newly designed adjuvants to improve the efficacy and safety of allergen immunotherapy. A better understanding of immunological mechanisms and further clinical trials utilizing new adjuvants are needed.

Adjuvants, Immunologic↗
PubMed2001

A Th1-inducing adjuvant, MPL, enhances antibody profiles in experimental animals suggesting it has the potential to improve the efficacy of allergy vaccines.

BACKGROUND: Monophosphoryl lipid A (MPL) is a detoxified derivative of the lipopolysaccharide (LPS) moiety of Salmonella minnesota R595, which has retained immunostimulatory activities. MPL has been administered to many subjects in clinical trials as an adjuvant component of infectious disease vaccines and is currently a component of a licensed cancer vaccine, Melacine (Corixa Inc., Schering Plough). MPL has, in particular, been shown to promote Th1-type antigen specific responses. L-tyrosine is a depot adjuvant which is fully metabolisable and has been successfully employed in allergy vaccines for a number of years. METHODS: Mice were immunised with MPL adjuvant in conjunction with separate preparations of either ovalbumin or glutaraldehyde-modified ragweed pollen extract both coprecipitated with L-tyrosine. The specific antibody isotypes IgG1, IgG2a, IgG2b and also IgE were measured. Rats received booster injections of keyhole limpet haemocyanin (KLH) in conjunction with MPL adjuvant following priming with KLH in alum alone. KLH-specific antibody responses were measured. RESULTS: It was shown that a combination of L-tyrosine and MPL were synergistic in enhancing murine antigen specific IgG antibody responses without enhancing antigen specific IgE responses. Furthermore, this adjuvant combination promoted strong IgG2 antigen specific responses indicative of a Th1 directed response. In KLH sensitised rats, treatment with MPL was shown to prevent a secondary IgE antibody response when injected with booster injections of antigen. CONCLUSIONS: Immunisation of mice with two different antigens adsorbed to L-tyrosine induced a Th1-skewed primary response when in conjunction with MPL adjuvant which also generally enhances a specific IgG response. Incorporation of MPL adjuvant in the immunisation of rats prevented a secondary specific IgE response. These results suggest that the employment of this new adjuvant in clinical allergy vaccination formulations may result in an improved efficacy which could be utilised in various ways to improve compliance.

Adjuvants, Immunologic↗
PubMed2006

Pollinex Quattro: a novel and well-tolerated, ultra short-course allergy vaccine.

Pollinex Quattro is a novel, ultra short-course vaccine for treatment of seasonal allergic rhinitis from grass, tree or ragweed pollen allergy. Its unique formulation combines chemically modified allergens adsorbed onto a L-tyrosine depot to enhance tolerability with the novel adjuvant, monophosphoryl lipid A, to improve efficacy. Controlled clinical studies indicate that four preseasonal injections with grass or tree formulations significantly reduce rhinoconjunctivitis symptoms and medication use, as well as elevate allergen-specific immunoglobulin G and blunt elevation of immunoglobulin E upon allergen exposure. Postmarketing surveillance studies indicate similar clinical outcomes. In all cases, the allergy vaccine was well tolerated with minimal local reactions, while systemic reactions were rare and mild. Results from recent investigational trials with grass and ragweed formulations are consistent with previous efficacy and safety outcomes, and will be used toward product registration in North America.

Adjuvants, Immunologic↗