Construction by artificial intelligence and immunovalidation of hypoallergenic mite allergen Der f 36 vaccine
BackgroundThe house dust mite (HDM) is widely recognized as the most prevalent allergen in allergic diseases. Allergen-specific immunotherapy (AIT) has been successfully implemented in clinical treatment for HDM. Hypoallergenic B-cell epitope-based vaccine designed by artificial intelligence (AI) re...
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| Format: | Article |
| Language: | English |
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Frontiers Media S.A.
2024-03-01
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| Series: | Frontiers in Immunology |
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| Online Access: | https://www.frontiersin.org/articles/10.3389/fimmu.2024.1325998/full |
| _version_ | 1797242913895219200 |
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| author | Qiao-Zhi Qin Qiao-Zhi Qin Jian Tang Cai-Yun Wang Zhi-Qiang Xu Zhi-Qiang Xu Man Tian |
| author_facet | Qiao-Zhi Qin Qiao-Zhi Qin Jian Tang Cai-Yun Wang Zhi-Qiang Xu Zhi-Qiang Xu Man Tian |
| author_sort | Qiao-Zhi Qin |
| collection | DOAJ |
| description | BackgroundThe house dust mite (HDM) is widely recognized as the most prevalent allergen in allergic diseases. Allergen-specific immunotherapy (AIT) has been successfully implemented in clinical treatment for HDM. Hypoallergenic B-cell epitope-based vaccine designed by artificial intelligence (AI) represents a significant progression of recombinant hypoallergenic allergen derivatives.MethodThe three-dimensional protein structure of Der f 36 was constructed using Alphafold2. AI-based tools were employed to predict B-cell epitopes, which were subsequently verified through IgE-reaction testing. Hypoallergenic Der f 36 was then synthesized, expressed, and purified. The reduced allergenicity was assessed by enzyme-linked immunosorbent assay (ELISA), immunoblotting, and basophil activation test. T-cell response to hypoallergenic Der f 36 and Der f 36 was evaluated based on cytokine expression in the peripheral blood mononuclear cells (PBMCs) of patients. The immunogenicity was evaluated and compared through rabbit immunization with hypoallergenic Der f 36 and Der f 36, respectively. The inhibitory effect of the blocking IgG antibody on the specific IgE-binding activity and basophil activation of Der f 36 allergen was also examined.ResultsThe final selected non-allergic B-cell epitopes were 25–48, 57–67, 107–112, 142–151, and 176–184. Hypoallergenic Der f 36 showed significant reduction in IgE-binding activity. The competitive inhibition of IgE-binding to Der f 36 was investigated using the hypoallergenic Der f 36, and only 20% inhibition could be achieved, which is greatly reduced when compared with inhibition by Der f 36 (98%). The hypoallergenic Der f 36 exhibited a low basophil-stimulating ratio similar to that of the negative control, and it could induce an increasing level of IFN‐γ but not Th2 cytokines IL-5 and IL-13 in PBMCs. The vaccine-specific rabbit blocking IgG antibodies could inhibit the patients’ IgE binding and basophil stimulation activity of Derf 36.ConclusionThis study represents the first application of an AI strategy to facilitate the development of a B-cell epitope-based hypoallergenic Der f 36 vaccine, which may become a promising immunotherapy for HDM-allergic patients due to its reduced allergenicity and its high immunogenicity in inducing blocking of IgG. |
| first_indexed | 2024-04-24T18:46:47Z |
| format | Article |
| id | doaj.art-d62357ef17aa49269283484371ea892d |
| institution | Directory Open Access Journal |
| issn | 1664-3224 |
| language | English |
| last_indexed | 2024-04-24T18:46:47Z |
| publishDate | 2024-03-01 |
| publisher | Frontiers Media S.A. |
| record_format | Article |
| series | Frontiers in Immunology |
| spelling | doaj.art-d62357ef17aa49269283484371ea892d2024-03-27T05:07:45ZengFrontiers Media S.A.Frontiers in Immunology1664-32242024-03-011510.3389/fimmu.2024.13259981325998Construction by artificial intelligence and immunovalidation of hypoallergenic mite allergen Der f 36 vaccineQiao-Zhi Qin0Qiao-Zhi Qin1Jian Tang2Cai-Yun Wang3Zhi-Qiang Xu4Zhi-Qiang Xu5Man Tian6Department of Respiratory Medicine, Children’s Hospital of Nanjing Medical University, Nanjing, ChinaPediatric Department, Northern Jiangsu People’s Hospital, Yangzhou, ChinaDepartment of Pharmacy, The Affiliated Cancer Hospital of Nanjing Medical University and Jiangsu Cancer Hospital and Jiangsu Institute of Cancer Research, Nanjing, ChinaDepartment of Respiratory Medicine, Children’s Hospital of Nanjing Medical University, Nanjing, ChinaResearch Division of Clinical Pharmacology, The First Affiliated Hospital of Nanjing Medical University, Nanjing, ChinaNational Vaccine Innovation Platform, Nanjing Medical University, Nanjing, ChinaDepartment of Respiratory Medicine, Children’s Hospital of Nanjing Medical University, Nanjing, ChinaBackgroundThe house dust mite (HDM) is widely recognized as the most prevalent allergen in allergic diseases. Allergen-specific immunotherapy (AIT) has been successfully implemented in clinical treatment for HDM. Hypoallergenic B-cell epitope-based vaccine designed by artificial intelligence (AI) represents a significant progression of recombinant hypoallergenic allergen derivatives.MethodThe three-dimensional protein structure of Der f 36 was constructed using Alphafold2. AI-based tools were employed to predict B-cell epitopes, which were subsequently verified through IgE-reaction testing. Hypoallergenic Der f 36 was then synthesized, expressed, and purified. The reduced allergenicity was assessed by enzyme-linked immunosorbent assay (ELISA), immunoblotting, and basophil activation test. T-cell response to hypoallergenic Der f 36 and Der f 36 was evaluated based on cytokine expression in the peripheral blood mononuclear cells (PBMCs) of patients. The immunogenicity was evaluated and compared through rabbit immunization with hypoallergenic Der f 36 and Der f 36, respectively. The inhibitory effect of the blocking IgG antibody on the specific IgE-binding activity and basophil activation of Der f 36 allergen was also examined.ResultsThe final selected non-allergic B-cell epitopes were 25–48, 57–67, 107–112, 142–151, and 176–184. Hypoallergenic Der f 36 showed significant reduction in IgE-binding activity. The competitive inhibition of IgE-binding to Der f 36 was investigated using the hypoallergenic Der f 36, and only 20% inhibition could be achieved, which is greatly reduced when compared with inhibition by Der f 36 (98%). The hypoallergenic Der f 36 exhibited a low basophil-stimulating ratio similar to that of the negative control, and it could induce an increasing level of IFN‐γ but not Th2 cytokines IL-5 and IL-13 in PBMCs. The vaccine-specific rabbit blocking IgG antibodies could inhibit the patients’ IgE binding and basophil stimulation activity of Derf 36.ConclusionThis study represents the first application of an AI strategy to facilitate the development of a B-cell epitope-based hypoallergenic Der f 36 vaccine, which may become a promising immunotherapy for HDM-allergic patients due to its reduced allergenicity and its high immunogenicity in inducing blocking of IgG.https://www.frontiersin.org/articles/10.3389/fimmu.2024.1325998/fullhouse dust mitehypoallergenic vaccineDer f 36artificial intelligenceB cell epitopes |
| spellingShingle | Qiao-Zhi Qin Qiao-Zhi Qin Jian Tang Cai-Yun Wang Zhi-Qiang Xu Zhi-Qiang Xu Man Tian Construction by artificial intelligence and immunovalidation of hypoallergenic mite allergen Der f 36 vaccine Frontiers in Immunology house dust mite hypoallergenic vaccine Der f 36 artificial intelligence B cell epitopes |
| title | Construction by artificial intelligence and immunovalidation of hypoallergenic mite allergen Der f 36 vaccine |
| title_full | Construction by artificial intelligence and immunovalidation of hypoallergenic mite allergen Der f 36 vaccine |
| title_fullStr | Construction by artificial intelligence and immunovalidation of hypoallergenic mite allergen Der f 36 vaccine |
| title_full_unstemmed | Construction by artificial intelligence and immunovalidation of hypoallergenic mite allergen Der f 36 vaccine |
| title_short | Construction by artificial intelligence and immunovalidation of hypoallergenic mite allergen Der f 36 vaccine |
| title_sort | construction by artificial intelligence and immunovalidation of hypoallergenic mite allergen der f 36 vaccine |
| topic | house dust mite hypoallergenic vaccine Der f 36 artificial intelligence B cell epitopes |
| url | https://www.frontiersin.org/articles/10.3389/fimmu.2024.1325998/full |
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