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Wise et al.

Page 124

New advances in AIT have focused on redirecting the untoward allergic diathesis through upregulation of T-regulatory and B-regulatory cells, restoring the balance between Th2 and Th1 cell subtypes, and establishing T-cell immune tolerance. The use of recombinant derived allergens, synthetic peptides, allergoids, and adjuvants has been sought to provide safer, more consistent, readily available, and effective allergens compared to commercially available native extracts 1580-1582 (Table IX.D.2-1). The laboratory production of allergens allows for modification of extracts and epitope structures that aim to enhance immunogenicity while decreasing the risk of adverse reactions. Clinical studies have reported outcomes for AIT using recombinant-produced molecules, synthetically-produced peptides, and modifications of allergens via allergoids with adjuvant molecules or through denaturing of proteins. Recombinant allergens.: Recombinant-derived allergens are produced by cloning of native allergen proteins with use of recombinant DNA technology. The allergy protein is reverse transcribed to yield a complimentary DNA molecule which can then be transferred into bacteria which produce copies of the incorporated DNA. This technique allows for controlled production of a high-yield product with consistent structure. Immunotherapy trials with recombinant allergens has been reported for birch pollen and Timothy grass pollen (Table IX.D.2-2). Recombinant birch AIT demonstrated equivalent clinical outcomes to native birch extract and improved symptoms over placebo. 1583-1585 Recombinant Timothy grass AIT showed improved outcomes compared to placebo with a good safety profile. 805,1586 Recently, a recombinant peptide carrier fusion grass vaccine has reported positive outcomes with a B-cell epitope-based vaccine for immunotherapy of grass pollen allergy. 798 • Aggregate Grade of Evidence for birch: B (Level 1b: 3 studies; Level 2b: 1 study). • Aggregate Grade of Evidence for Timothy grass: B (Level 1b: 3 studies). • These studies of recombinant allergens for birch and Timothy grass demonstrate safety and efficacy. Peptide constructs. Synthetic peptides for immunotherapy are linear fragments of amino acids that correspond to T-cell epitopes. These fragments lack the secondary and tertiary structure that activate IgE receptors, but can induce immunologic tolerance by targeting allergen-specific T-cells to induce tolerance. The premise with synthetic peptides is that the lack of IgE activation will eliminate the risk of IgE-mediated adverse reaction while preserving the immunogenicity that leads to desensitization. AIT trials with synthetic peptides have been reported for cat, birch, and ragweed allergens (Table IX.D.2-2). Overall, studies have shown mixed outcomes from synthetic peptides with some peptide molecules resulting in an increase in late adverse reactions. The recently completed large-scale multicenter field trial (https://clinicaltrials.gov/ct2/show/NCT01620762; Phase III Cat-PAD Study) with cat peptide failed; however, as of this writing, the HDM peptide study is ongoing. 1587,1588 Newer peptide constructs under investigation include overlapping peptides that reproduce the entire sequence of the naturally-occurring allergen in an attempt to cover all T-cell epitopes and natural peptide fragments that cover a broad panel of epitopes. 1589

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Int Forum Allergy Rhinol . Author manuscript; available in PMC 2020 June 10.