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Randomized Controlled Trial
. 2025 Nov;156(5):1303-1313.
doi: 10.1016/j.jaci.2025.07.011. Epub 2025 Jul 24.

Cockroach immunotherapy modulates dominant T-cell responses independent of allergen extract content

Ricardo da Silva Antunes  1 , Aaron Sutherland  1 , Adam Abawi  1 , April Frazier  1 , Anna Pomés  2 , Jill Glesner  2 , Jay E Slater  3 , Samuel T Mindaye  3 , Kate Cho  4 , Grace Zhou  4 , Marie V Ozanne  4 , Agustin Calatroni  4 , Cynthia M Visness  4 , Matthew C Altman  5 , Robert A Wood  6 , George T O'Connor  7 , Jacqueline A Pongracic  8 , Gurjit K Khurana Hershey  9 , Carolyn M Kercsmar  10 , Rebecca S Gruchalla  11 , Michelle Gill  11 , Daniel Searing  12 , Andrew H Liu  12 , Edward Zoratti  13 , Meyer Kattan  14 , Paula J Busse  15 , Will Sheehan  16 , Leonard B Bacharier  16 , Stephen J Teach  17 , Lisa M Wheatley  18 , Alkis Togias  18 , William W Busse  19 , Daniel J Jackson  19 , Alessandro Sette  20
Affiliations
Randomized Controlled Trial

Cockroach immunotherapy modulates dominant T-cell responses independent of allergen extract content

Ricardo da Silva Antunes et al. J Allergy Clin Immunol. 2025 Nov.

Abstract

Background: T-cell responses to the individual components of allergen extracts have not been fully elucidated in subcutaneous allergen immunotherapy (SCIT). Specifically, it is unknown whether T-cell responses to immunodominant allergens are more or less sensitive to modulation, and whether allergen abundance in the immunotherapy extract influences T-cell response modulation.

Objective: To fill these gaps, we evaluated CD4+ T-cell reactivity specific to each of the main cockroach allergens in the double-blinded, placebo controlled, multicenter CRITICAL (NCT03541187) SCIT trial.

Methods: Participants aged 8-17 years with mild-to-moderate, well-controlled asthma received 12 months' dosing with cockroach SCIT (n = 20) or placebo (n = 26). Peripheral blood mononuclear cells were isolated before and after 12 months of therapy. CD4+ T-cell responses at baseline and after treatment were assessed using overlapping peptide pools derived from 11 well-defined cockroach allergens and intracellular cytokine staining for IL-4, IFN-γ, and IL-10 production. T-cell responses were evaluated for magnitude, cytokine polarization, allergen immunodominance, and correlation with allergen content in the cockroach SCIT extract.

Results: SCIT modulation was more prominent in participants with the strongest and most TH2-polarized responses. Downmodulation was observed against Bla g 5 and Bla g 9, the most dominantly recognized allergens in the population study. Furthermore, effective modulation was observed independent of allergen content in the cockroach SCIT extract.

Conclusion: Immunodominant responses are effectively modulated by SCIT, and this effect is independent of allergen abundance in the extract utilized for SCIT.

Keywords: Allergens; T cell; cockroach; extract; immunodominance; immunotherapy.

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Conflict of interest statement

Disclosure statement Funded in whole or part with federal funds from the National Institute of Allergy and Infectious Diseases, National Institutes of Health (NIH), Department of Health and Human Services, under grants 1UM1AI114271-01, UM2AI117870, and 5UM1AI114271-03. Additional support was provided by the National Center for Research Resources, and National Center for Advancing Translational Sciences, NIH, under grants NCATS/NIH UL1TR001079, NCATS/NIH UL1TR001422, NCATS/NIH UL1TR001876, NIH/CTSA 5UL1TR001425-03, and NIAID/NIH U19AI135731. Disclosure of potential conflict of interest: The authors declare that they have no relevant conflicts of interest.

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