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B-cell epitope peptide immunotherapy alleviates chitin-binding protein-induced type 2 airway inflammation in a Blomia
Jiale Zhang1,2, Wenting Luo1,2, YuBao Cui3
1Department of Clinical Laboratory, National Center for Respiratory Medicine, National Clinical Research Center for Respiratory Disease, State Key Laboratory of Respiratory Disease, Guangzhou Institute of Respiratory Health, The First Affiliated Hospital of Guangzhou Medical University, Guangzhou, Guangdong, 510120, China.
Background:
Peptide immunotherapy (PIT) offers a safe and effective treatment with minimal side effects. This study aims to identify B-cell epitopes of a novel allergen from Blomia tropicalis (B. tropicalis), specifically the Chitin-binding domain type 2 (ChtBD2) protein, and evaluate the therapeutic effects of peptide treatment in a murine model.
Methods:
Using Alphafold2, the 3D structure of ChtBD2 was constructed. AI-based and traditional computational tools predicted the predominant B-cell epitopes. Twelve synthesized peptides were assessed for allergenicity and immunogenicity. A murine model of B. tropicalis-induced allergic airway inflammation mimicking human atopic asthma was developed and analyzed.
Results:
Predominant B-cell epitopes of ChtBD2 were identified as promising IgE-binding domains. Peptide 1 (PT1: 1-15) showed significant IgE-binding activity and the highest inhibition rate in competitive IgE-binding assays. PT1 upregulated IL-4, IL-13, and CD63 in B. tropicalis-sensitized patients' PBMCs and basophils, respectively. Notably, IT groups showed reduced lung cellular infiltration and type 2 cytokine expression in BALF. Specific IgE levels were reduced, with a decline in the IgG1/IgG2a ratio.
Conclusions:
This study represents the first AI-facilitated development of a B-cell epitope-based ChtBD2 PIT, showing promise as an immunotherapy for B. tropicalis-allergic patients with reduced allergenicity and high immunogenicity in inducing IgG-blocking antibodies.
Clinical Trial:
Not applicable.
