Preparation and Analysis of Peanut Flour Used in Oral Immunotherapy Clinical Trials

Overview

Journal J Allergy Clin Immunol Pract

Specialty Allergy & Immunology

Date 2017 Jan 31

PMID 28132800

Citations 13

Authors

Jelena P Berglund

Nicole Szczepanski

Anusha Penumarti

Ayeshia Beavers

Janelle Kesselring

Kelly Orgel

Bruce Burnett

A Wesley Burks

Michael Kulis

Affiliations

Soon will be listed here.

Abstract

Background: Oral immunotherapy (OIT) is an investigational therapeutic approach for the treatment of food allergies. Characterization of the drug product used in oral immunotherapy trials for peanut allergy has not been reported.

Objective: To quantify relative amounts of the major peanut allergens and microbial load present in peanut flour used in OIT trials and assess whether these parameters change over a 12-month period. We also anticipate that this report will serve as a guide for investigators seeking to conduct OIT trials under Food and Drug Administration-approved Investigational New Drug applications.

Methods: Densitometric scanning of Ara h 1 and Ara h 2 resolved on SDS-PAGE gels was used to assess allergen content in peanut flour extracts. Microbial testing was conducted on peanut flour under US Pharmacopeia guidelines for the presence of Escherichia coli, salmonella, yeast, mold, and total aerobic bacteria. In addition, aflatoxin was quantified in peanut flour. Reported results were obtained from 4 unique lots of peanut flour.

Results: Relative amounts of the major peanut allergens were similar between different lots of peanut flour and remained stable over a 12-month period. E coli and salmonella were absent from all lots of flour. Yeast, mold, total aerobic bacteria, and aflatoxin were within established US Pharmacopeia guidelines on all lots tested and remained within the criteria over a 12-month period.

Conclusions: Peanut flour used as a drug product contains the major peanut allergens and has low levels of potentially harmful microbes. Both these parameters remain stable over a 12-month period.

Citing Articles

Affordable oral proinsulin bioencapsulated in plant cells regulates blood sugar levels similar to natural insulin.

Daniell H, Singh R, Mangu V, Nair S, Wakade G, Balashova N Biomaterials. 2023; 298:122142.

PMID: 37148757 PMC: 10219636. DOI: 10.1016/j.biomaterials.2023.122142.

Kinetics of basophil hyporesponsiveness during short-course peanut oral immunotherapy.

Kulis M, Smeekens J, Burk C, Yue X, Guo R, Orgel K J Allergy Clin Immunol. 2022; 150(5):1144-1153.

PMID: 35716952 PMC: 9643597. DOI: 10.1016/j.jaci.2022.05.020.

Efficacy and safety of oral immunotherapy in children aged 1-3 years with peanut allergy (the Immune Tolerance Network IMPACT trial): a randomised placebo-controlled study.

Jones S, Kim E, Nadeau K, Nowak-Wegrzyn A, Wood R, Sampson H Lancet. 2022; 399(10322):359-371.

PMID: 35065784 PMC: 9119642. DOI: 10.1016/S0140-6736(21)02390-4.

Debulking SARS-CoV-2 in saliva using angiotensin converting enzyme 2 in chewing gum to decrease oral virus transmission and infection.

Daniell H, Nair S, Esmaeili N, Wakade G, Shahid N, Ganesan P Mol Ther. 2021; 30(5):1966-1978.

PMID: 34774754 PMC: 8580552. DOI: 10.1016/j.ymthe.2021.11.008.

From Allergen Molecules to Molecular Immunotherapy of Nut Allergy: A Hard Nut to Crack.

Fuhrmann V, Huang H, Akarsu A, Shilovskiy I, Elisyutina O, Khaitov M Front Immunol. 2021; 12:742732.

PMID: 34630424 PMC: 8496898. DOI: 10.3389/fimmu.2021.742732.

References

Anagnostou K, Clark A, King Y, Islam S, Deighton J, Ewan P . Efficacy and safety of high-dose peanut oral immunotherapy with factors predicting outcome. Clin Exp Allergy. 2011; 41(9):1273-81. DOI: 10.1111/j.1365-2222.2011.03699.x. View

Nowak-Wegrzyn A, Sampson H . Future therapies for food allergies. J Allergy Clin Immunol. 2011; 127(3):558-73. PMC: 3066474. DOI: 10.1016/j.jaci.2010.12.1098. View

Keet C, Frischmeyer-Guerrerio P, Thyagarajan A, Schroeder J, Hamilton R, Boden S . The safety and efficacy of sublingual and oral immunotherapy for milk allergy. J Allergy Clin Immunol. 2011; 129(2):448-55, 455.e1-5. PMC: 3437605. DOI: 10.1016/j.jaci.2011.10.023. View

Skripak J, Nash S, Rowley H, Brereton N, Oh S, Hamilton R . A randomized, double-blind, placebo-controlled study of milk oral immunotherapy for cow's milk allergy. J Allergy Clin Immunol. 2008; 122(6):1154-60. PMC: 3764488. DOI: 10.1016/j.jaci.2008.09.030. View

Bublin M, Kostadinova M, Radauer C, Hafner C, Szepfalusi Z, Varga E . IgE cross-reactivity between the major peanut allergen Ara h 2 and the nonhomologous allergens Ara h 1 and Ara h 3. J Allergy Clin Immunol. 2013; 132(1):118-24. DOI: 10.1016/j.jaci.2013.01.022. View

Shi X, Guo R, White B, Yancey A, Sanders T, Davis J . Allergenic properties of enzymatically hydrolyzed peanut flour extracts. Int Arch Allergy Immunol. 2013; 162(2):123-30. DOI: 10.1159/000351920. View

Jones S, Pons L, Roberts J, Scurlock A, Perry T, Kulis M . Clinical efficacy and immune regulation with peanut oral immunotherapy. J Allergy Clin Immunol. 2009; 124(2):292-300, 300.e1-97. PMC: 2725434. DOI: 10.1016/j.jaci.2009.05.022. View

Prickett S, Voskamp A, Phan T, Dacumos-Hill A, Mannering S, Rolland J . Ara h 1 CD4+ T cell epitope-based peptides: candidates for a peanut allergy therapeutic. Clin Exp Allergy. 2013; 43(6):684-97. PMC: 3709139. DOI: 10.1111/cea.12113. View

Li J, Bernstein D, Calderon M, Casale T, Cox L, Passalacqua G . Sublingual grass and ragweed immunotherapy: Clinical considerations-a PRACTALL consensus report. J Allergy Clin Immunol. 2015; 137(2):369-76. DOI: 10.1016/j.jaci.2015.06.046. View

10.

Burks A, Jones S, Wood R, Fleischer D, Sicherer S, Lindblad R . Oral immunotherapy for treatment of egg allergy in children. N Engl J Med. 2012; 367(3):233-43. PMC: 3424505. DOI: 10.1056/NEJMoa1200435. View

11.

Vickery B, Scurlock A, Kulis M, Steele P, Kamilaris J, Berglund J . Sustained unresponsiveness to peanut in subjects who have completed peanut oral immunotherapy. J Allergy Clin Immunol. 2013; 133(2):468-75. PMC: 3960331. DOI: 10.1016/j.jaci.2013.11.007. View

12.

Vickery B, Lin J, Kulis M, Fu Z, Steele P, Jones S . Peanut oral immunotherapy modifies IgE and IgG4 responses to major peanut allergens. J Allergy Clin Immunol. 2012; 131(1):128-34.e1-3. PMC: 3529994. DOI: 10.1016/j.jaci.2012.10.048. View

13.

Burks A, Williams L, Helm R, Connaughton C, Cockrell G, OBrien T . Identification of a major peanut allergen, Ara h I, in patients with atopic dermatitis and positive peanut challenges. J Allergy Clin Immunol. 1991; 88(2):172-9. DOI: 10.1016/0091-6749(91)90325-i. View

14.

Varshney P, Jones S, Scurlock A, Perry T, Kemper A, Steele P . A randomized controlled study of peanut oral immunotherapy: clinical desensitization and modulation of the allergic response. J Allergy Clin Immunol. 2011; 127(3):654-60. PMC: 3060783. DOI: 10.1016/j.jaci.2010.12.1111. View

15.

Jutel M, Agache I, Bonini S, Burks A, Calderon M, Canonica W . International consensus on allergy immunotherapy. J Allergy Clin Immunol. 2015; 136(3):556-68. DOI: 10.1016/j.jaci.2015.04.047. View

16.

Burks A . Peanut allergy. Lancet. 2008; 371(9623):1538-46. DOI: 10.1016/S0140-6736(08)60659-5. View

17.

Schmitt D, Nesbit J, Hurlburt B, Cheng H, Maleki S . Processing can alter the properties of peanut extract preparations. J Agric Food Chem. 2009; 58(2):1138-43. DOI: 10.1021/jf902694j. View

18.

Porterfield H, Murray K, Schlichting D, Chen X, Hansen K, Duncan M . Effector activity of peanut allergens: a critical role for Ara h 2, Ara h 6, and their variants. Clin Exp Allergy. 2009; 39(7):1099-108. PMC: 2752635. DOI: 10.1111/j.1365-2222.2009.03273.x. View

19.

Wood R, Sicherer S, Burks A, Grishin A, Henning A, Lindblad R . A phase 1 study of heat/phenol-killed, E. coli-encapsulated, recombinant modified peanut proteins Ara h 1, Ara h 2, and Ara h 3 (EMP-123) for the treatment of peanut allergy. Allergy. 2013; 68(6):803-8. PMC: 3663889. DOI: 10.1111/all.12158. View

20.

Oppenheimer J, Nelson H, Bock S, Christensen F, Leung D . Treatment of peanut allergy with rush immunotherapy. J Allergy Clin Immunol. 1992; 90(2):256-62. DOI: 10.1016/0091-6749(92)90080-l. View