Investigation of peanut oral immunotherapy with CpG/peanut nanoparticles in a murine model of peanut allergy Kamal D. Srivastava, PhD, Alyssa Siefert,

Slides:

Advertisements

Similar presentations

Peter Vadas, MD, PhD, Boris Perelman, PhD, Gary Liss, MD, MS

Advertisements

Dose-time-response relationship in peanut allergy using a human model of passive cutaneous anaphylaxis Anja P. Mose, MD, Charlotte G. Mortz, MD, PhD,

Repeated low-dose intradermal allergen injection suppresses allergen-induced cutaneous late responses Giuseppina Rotiroti, MD, Mohamed Shamji, PhD, Stephen.

The use of serum-specific IgE measurements for the diagnosis of peanut, tree nut, and seed allergy Jennifer M. Maloney, MD, Magnus Rudengren, BSc, Staffan.

A randomized, double-blind, placebo-controlled pilot study of sublingual versus oral immunotherapy for the treatment of peanut allergy Satya D. Narisety,

Therapeutic reversal of food allergen sensitivity by mature retinoic acid–differentiated dendritic cell induction of LAG3+CD49b−Foxp3− regulatory T cells

Selective ablation of mast cells or basophils reduces peanut-induced anaphylaxis in mice Laurent L. Reber, PhD, Thomas Marichal, DVM, PhD, Kaori Mukai,

IgE-mediated systemic anaphylaxis and impaired tolerance to food antigens in mice with enhanced IL-4 receptor signaling Clinton B. Mathias, PhD, Suejy.

Jay A. Lieberman, MD, Faith R. Huang, MD, Hugh A

Odelya E. Pagovich, MD, Bo Wang, MD, Maria J

Maternal allergy increases susceptibility to offspring allergy in association with TH2- biased epigenetic alterations in a mouse model of peanut allergy

Blocking antibodies induced by immunization with a hypoallergenic parvalbumin mutant reduce allergic symptoms in a mouse model of fish allergy Raphaela.

Allergic sensitization can be induced via multiple physiologic routes in an adjuvant- dependent manner David Dunkin, MD, M. Cecilia Berin, PhD, Lloyd.

Oral immunotherapy induces IgG antibodies that act through FcγRIIb to suppress IgE- mediated hypersensitivity Oliver T. Burton, PhD, Stephanie L. Logsdon,

Ramipril and metoprolol intake aggravate human and murine anaphylaxis: Evidence for direct mast cell priming Maria Nassiri, MS, Magda Babina, PhD, Sabine.

Safety, clinical, and immunologic efficacy of a Chinese herbal medicine (Food Allergy Herbal Formula-2) for food allergy Julie Wang, MD, Stacie M. Jones,

Epicutaneous sensitization results in IgE-dependent intestinal mast cell expansion and food-induced anaphylaxis Lisa M. Bartnikas, MD, Michael F. Gurish,

Matthew C. Tunis, BSc, Wojciech Dawicki, PhD, Kaitlyn R

Odelya E. Pagovich, MD, Bo Wang, MD, Maria J

Forkhead box protein 3 demethylation is associated with tolerance induction in peanut- induced intestinal allergy Meiqin Wang, MD, PhD, Ivana V. Yang,

Differential roles for the IL-9/IL-9 receptor α-chain pathway in systemic and oral antigen–induced anaphylaxis Heather Osterfeld, BSc, Richard Ahrens,

A randomized controlled study of peanut oral immunotherapy: Clinical desensitization and modulation of the allergic response Pooja Varshney, MD, Stacie.

Specific epicutaneous immunotherapy prevents sensitization to new allergens in a murine model Lucie Mondoulet, PhD, Vincent Dioszeghy, PhD, Emilie Puteaux,

Allergy testing in predicting outcome of open food challenge to peanut

Distinct immune effector pathways contribute to the full expression of peanut-induced anaphylactic reactions in mice Katherine Arias, BHSc, Derek K.

A randomized, double-blind, placebo-controlled study of milk oral immunotherapy for cow's milk allergy Justin M. Skripak, MD, Scott D. Nash, MD, Hannah.

Persistent protective effect of heat-killed Escherichia coli producing “engineered,” recombinant peanut proteins in a murine model of peanut allergy

Ellen Mueller Fox, PhD, Marina N

Oral immunotherapy induces local protective mechanisms in the gastrointestinal mucosa Stephanie A. Leonard, MD, Gustavo Martos, PhD, Wei Wang, MD, Anna.

Single–tree nut immunotherapy attenuates allergic reactions in mice with hypersensitivity to multiple tree nuts Mike Kulis, PhD, Yifan Li, BS, Hannah.

Food allergy herbal formula 2 protection against peanut anaphylactic reaction is via inhibition of mast cells and basophils Ying Song, MD, Chunfeng Qu,

Prostaglandin E2 suppresses allergic sensitization and lung inflammation by targeting the E prostanoid 2 receptor on T cells Zbigniew Zasłona, PhD, Katsuhide.

Takao Kobayashi, PhD, Koji Iijima, PhD, Alexander L

Food Allergy Herbal Formula-2 silences peanut-induced anaphylaxis for a prolonged posttreatment period via IFN-γ–producing CD8+ T cells Kamal D. Srivastava,

Iván López-Expósito, PhD, Ying Song, MD, Kirsi M

A randomized, double-blind, placebo-controlled pilot study of sublingual versus oral immunotherapy for the treatment of peanut allergy Satya D. Narisety,

IgE-class–specific immunosuppression in offspring by administration of anti-IgE to pregnant mice Hideaki Morita, MD, PhD, Masato Tamari, MD, PhD, Masako.

Peanut-induced intestinal allergy is mediated through a mast cell–IgE–FcεRI–IL-13 pathway Meiqin Wang, MD, PhD, Katsuyuki Takeda, MD, PhD, Yoshiki Shiraishi,

A. Wesley Burks, MD, Robert A. Wood, MD, Stacie M. Jones, MD, Scott H

Laurent Pons, PhD, Usha Ponnappan, PhD, Renée A

Induction of long-lived allergen-specific plasma cells by mucosal allergen challenge Elke O. Luger, PhD, Verena Fokuhl, MSc, Michael Wegmann, PhD, Melanie.

Orally administered TGF-β is biologically active in the intestinal mucosa and enhances oral tolerance Takashi Ando, MD, PhD, Kyosuke Hatsushika, MD,

Food allergy: A review and update on epidemiology, pathogenesis, diagnosis, prevention, and management Scott H. Sicherer, MD, Hugh A. Sampson, MD Journal.

Oral administration of a synthetic agonist of Toll-like receptor 9 potently modulates peanut-induced allergy in mice Fu-Gang Zhu, PhD, Ekambar R. Kandimalla,

Kirthana Ganeshan, BS, Colleen V

Peter Vadas, MD, PhD, Boris Perelman, PhD, Gary Liss, MD, MS

Dose-time-response relationship in peanut allergy using a human model of passive cutaneous anaphylaxis Anja P. Mose, MD, Charlotte G. Mortz, MD, PhD,

Ganglioside GQ1b enhances Ig production by human PBMCs

Allergen-specific sublingual immunotherapy is dose and duration dependent in a murine allergic rhinitis model Soichi Tofukuji, PhD, Kazufumi Katayama,

Genetic susceptibility to food allergy is linked to differential TH2-TH1 responses in C3H/HeJ and BALB/c mice Vivian Morafo, PhD*, Kamal Srivastava,

Food allergy: Epidemiology, pathogenesis, diagnosis, and treatment

Dietary medium-chain triglycerides promote oral allergic sensitization and orally induced anaphylaxis to peanut protein in mice Jianing Li, MS, Yu Wang,

The Chinese herbal medicine formula FAHF-2 completely blocks anaphylactic reactions in a murine model of peanut allergy Kamal D. Srivastava, MPhil, Jacob.

Safety, clinical, and immunologic efficacy of a Chinese herbal medicine (Food Allergy Herbal Formula-2) for food allergy Julie Wang, MD, Stacie M. Jones,

Eric B. Brandt, PhD, Ariel Munitz, PhD, Tatyana Orekov, MS, Melissa K

Efficacy and tolerability of antiasthma herbal medicine intervention in adult patients with moderate-severe allergic asthma Ming-Chun Wen, MD, Chun-Hua.

The steroidogenic enzyme Cyp11a1 is essential for development of peanut-induced intestinal anaphylaxis Meiqin Wang, MD, PhD, Julita Ramirez, DVM, PhD,

Xiu-Min Li, MD, LaVerne Brown, PhD

Blockade of peanut allergy with a novel Ara h 2–Fcγ fusion protein in mice Yu Liu, MD, PhD, Yongtao Sun, MD, PhD, Lee-Jah Chang, MD, Newton Li, MD, Huabin.

Grass pollen immunotherapy: IL-10 induction and suppression of late responses precedes IgG4 inhibitory antibody activity James N. Francis, PhD, Louisa.

Oral peanut immunotherapy in children with peanut anaphylaxis

Clinical safety of Food Allergy Herbal Formula-2 (FAHF-2) and inhibitory effect on basophils from patients with food allergy: Extended phase I study

Early improvement in basophil sensitivity predicts symptom relief with grass pollen immunotherapy Johannes Martin Schmid, MD, Peter Adler Würtzen, PhD,

Repeated low-dose intradermal allergen injection suppresses allergen-induced cutaneous late responses Giuseppina Rotiroti, MD, Mohamed Shamji, PhD, Stephen.

Epicutaneous immunization with ovalbumin and CpG induces TH1/TH17 cytokines, which regulate IgE and IgG2a production Monika Majewska-Szczepanik, PhD,

Placental transfer of allergen-specific IgG but not IgE from a specific immunotherapy– treated mother Sabine Flicker, PhD, Katharina Marth, MD, Heinz.

DNA-based vaccination reduces the risk of lethal anaphylactic hypersensitivity in mice Anthony A. Horner, MDa, Minh-Duc Nguyen, BAa, Arash Ronaghy, BAa,

Soybean isoflavones regulate dendritic cell function and suppress allergic sensitization to peanut Madhan Masilamani, PhD, John Wei, BA, Shiven Bhatt,

Sublingual immunotherapy for peanut allergy: Clinical and immunologic evidence of desensitization Edwin H. Kim, MD, J. Andrew Bird, MD, Michael Kulis,

The use of serum-specific IgE measurements for the diagnosis of peanut, tree nut, and seed allergy Jennifer M. Maloney, MD, Magnus Rudengren, BSc, Staffan.

Presentation transcript:

Investigation of peanut oral immunotherapy with CpG/peanut nanoparticles in a murine model of peanut allergy Kamal D. Srivastava, PhD, Alyssa Siefert, PhD, Tarek M. Fahmy, PhD, Michael J. Caplan, MD, Xiu-Min Li, MD, Hugh A. Sampson, MD Journal of Allergy and Clinical Immunology Volume 138, Issue 2, Pages 536-543.e4 (August 2016) DOI: 10.1016/j.jaci.2016.01.047 Copyright © 2016 American Academy of Allergy, Asthma & Immunology Terms and Conditions

Fig 1 Experimental design. Protocol for sensitization, treatment, and challenge: 6-week-old C3H/HEJ mice were orally sensitized with peanut (PN) and cholera toxin at weeks 0 through 5. Mice were boosted with peanut and cholera toxin at weeks 6 and 8. Weekly oral treatment started at week 11 (blue upward arrows) and continued through week 14. Mice underwent oral peanut challenge 5 days later and then at 4-week intervals for another 4 challenges (weeks 14, 18, 22, 26, and 30, as indicated by tall black arrows). Short black arrows indicate oral gavage with sensitization dose of peanut plus cholera toxin given 1 day after each challenge, except the final challenge at week 30. N = 10-22 mice per group from 2 separate experiments. i.g., Intragastric; NP, nanoparticles. Journal of Allergy and Clinical Immunology 2016 138, 536-543.e4DOI: (10.1016/j.jaci.2016.01.047) Copyright © 2016 American Academy of Allergy, Asthma & Immunology Terms and Conditions

Fig 2 Anaphylaxis symptom scores. Thirty minutes after oral peanut (PN) challenge, mice were visually assessed for symptoms of anaphylaxis and assigned symptom scores using the scoring system described in the Methods section. Naive mice were challenged only at the fifth challenge. Bars represent group medians. **P < .01 and ***P < .001 versus sham. N = 10-22 mice per group from 2 separate experiments. NC, Not challenged; NP, nanoparticles. Journal of Allergy and Clinical Immunology 2016 138, 536-543.e4DOI: (10.1016/j.jaci.2016.01.047) Copyright © 2016 American Academy of Allergy, Asthma & Immunology Terms and Conditions

Fig 3 Body temperature after oral peanut (PN) challenges. After recording symptom scores, the core body temperature of each animal was measured with a rectal thermometer. Data show group medians and interquartile range. *P < .05 and ***P < .001 versus sham. N = 10-22 mice per group from 2 separate experiments. NP, Nanoparticles. Journal of Allergy and Clinical Immunology 2016 138, 536-543.e4DOI: (10.1016/j.jaci.2016.01.047) Copyright © 2016 American Academy of Allergy, Asthma & Immunology Terms and Conditions

Fig 4 Plasma histamine levels after oral peanut (PN) challenge. Blood was drawn approximately 30 minutes after the oral peanut challenge, and plasma was harvested for measurement of histamine by using ELISA. Data are shown as means ± SDs at each of the 5 challenges. **P < .01 and ***P < .001 versus sham. N = 10-22 mice per group from 2 separate experiments. NP, Nanoparticles. Journal of Allergy and Clinical Immunology 2016 138, 536-543.e4DOI: (10.1016/j.jaci.2016.01.047) Copyright © 2016 American Academy of Allergy, Asthma & Immunology Terms and Conditions

Fig 5 Peanut (PN)–specific immunoglobulins. Blood was drawn from mice at the times indicated. Peanut-specific serum IgE (A), IgG1 (B), and IgG2a (C) levels were measured by using ELISA. Data symbols indicate group medians, and bars indicate interquartile ranges. *P < .05 and **P < .01 versus sham. N = 10-22 mice per group from 2 separate experiments. NP, Nanoparticles. Journal of Allergy and Clinical Immunology 2016 138, 536-543.e4DOI: (10.1016/j.jaci.2016.01.047) Copyright © 2016 American Academy of Allergy, Asthma & Immunology Terms and Conditions

Fig 6 Peanut (PN)–restimulated splenocyte cytokine levels. Splenocyte cultures from individual mice were incubated in the presence of 200 μg of peanut extract or medium alone for 72 hours under standard tissue culture conditions. Cytokine levels were measured by using ELISA. Data are displayed as group medians and interquartile ranges. ***P < .001 versus sham. N = 10-22 mice per group from 2 separate experiments. NP, Nanoparticles. Journal of Allergy and Clinical Immunology 2016 138, 536-543.e4DOI: (10.1016/j.jaci.2016.01.047) Copyright © 2016 American Academy of Allergy, Asthma & Immunology Terms and Conditions

Fig E1 Anaphylactic reactions to oral peanut (PN) challenge. A, Mice were visually assessed for symptoms of anaphylaxis 30 minutes after challenge and assigned symptom scores by using the scoring system described in the Methods section. Naive mice were challenged only at the fifth challenge. Bars represent group medians. B, Body temperatures were measured with a rectal thermometer. C, Histamine levels in plasma harvested after challenge were measured by using ELISA. Data are shown as means ± SDs. Bars indicate group medians in Fig E1, A, and group means ± SDs for Fig E1, B and C. *P < .05, **P < .01, and ***P < .001 versus sham. N = 5-10 mice per group. NP, Nanoparticles. Journal of Allergy and Clinical Immunology 2016 138, 536-543.e4DOI: (10.1016/j.jaci.2016.01.047) Copyright © 2016 American Academy of Allergy, Asthma & Immunology Terms and Conditions

Fig E2 Peanut (PN)–specific immunoglobulins. Blood was drawn before treatment (week 11) and each of the challenges (weeks 14-30). Peanut-specific serum IgE (A), IgG1 (B), and IgG2a (C) levels were measured by using ELISA. Symbols indicate group medians, and bars indicate interquartile ranges. **P < .01; ***P < .001 versus sham. N = 5-10 mice per group. NP, Nanoparticles. Journal of Allergy and Clinical Immunology 2016 138, 536-543.e4DOI: (10.1016/j.jaci.2016.01.047) Copyright © 2016 American Academy of Allergy, Asthma & Immunology Terms and Conditions

Fig E3 Peanut (PN)–restimulated splenocyte cytokine levels. Splenocyte cultures from individual mice were incubated in the presence of 200 μg of peanut extract or medium alone for 72 hours under standard tissue culture conditions. Cytokine levels were measured by using ELISA. Data show group medians and interquartile ranges. ***P < .001 versus sham. N = 5-10 mice per group. Journal of Allergy and Clinical Immunology 2016 138, 536-543.e4DOI: (10.1016/j.jaci.2016.01.047) Copyright © 2016 American Academy of Allergy, Asthma & Immunology Terms and Conditions