Author
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GREGORY, JAMES - Mount Sinai School Of Medicine |
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MCTAGGART, ARIEL - Mount Sinai School Of Medicine |
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UMPIERREZ, MICHELLE - Mount Sinai School Of Medicine |
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Hurlburt, Barry |
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Maleki, Soheila |
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SAMPSON, HUGH - Mount Sinai School Of Medicine |
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MAYFIELD, STEPHEN - University Of California |
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BERIN, CECILIA - Mount Sinai School Of Medicine |
Submitted to: Plant Biotechnology
Publication Type: Peer Reviewed Journal Publication Acceptance Date: 11/13/2015 Publication Date: 11/13/2015 Citation: Gregory, J., Mctaggart, A., Umpierrez, M., Hurlburt, B.K., Maleki, S.J., Sampson, H., Mayfield, S., Berin, C. 2015. Immunotherapy using algal-produced Ara h1 core domain suppresses peanut allergy in mice. Plant Biotechnology. 14(7):1541-1150. Interpretive Summary: Peanut allergy can cause a variety of medical reactions including death via anaphylaxis. There is currently no cure for the disease. Immunotherapy is currently the most plausible treatment. In this approach allergic patients are given small, non-reactive doses of the allergen with a subsequent increasing dose regimen. In the work described in this paper, allergens are produced in algae and tested for reactions in vitro. Algae were chosen because it would afford and cheap reliable source of allergen for immunotherapy. Technical Abstract: Peanut allergy is an IgE-mediated adverse reaction to a subset of proteins found in peanuts. Immunotherapy aims to desensitize allergic patients through repeated and escalating exposures for several months to years using extracts or flours. The complex mix of proteins and variability between preparations complicates immunotherapy studies. Moreover, peanut immunotherapy is associated with frequent negative side effects and patients are often at risk of allergic reactions once immunotherapy is discontinued. Allergen specific approaches using recombinant proteins are an attractive alternative because they allow more precise dosing and the opportunity to engineer proteins with improved safety profiles. We tested whether Ara h1 and Ara h2, two major peanut allergens, could be produced using chloroplast of the unicellular eukaryotic alga, Chlamydomonas reinhardtii. C. reinhardtii is novel host for producing allergens that is genetically tractable, inexpensive and easy to grow, and is able to produce more complex proteins than bacterial hosts. Compared to the native proteins, algal-produced Ara h1 core domain and Ara h2 have a reduced affinity for IgE from peanut allergic patients. We further found that immunotherapy using algal-Ara h1 core domain confers protection from peanut induced anaphylaxis in a murine model of peanut allergy. |