PMID- 35580444 OWN - NLM STAT- MEDLINE DCOM- 20220608 LR - 20220621 IS - 1878-3279 (Electronic) IS - 0171-2985 (Linking) VI - 227 IP - 3 DP - 2022 May TI - The development of a candidate of desensitization vaccines against Der f 2 nearly without IgE-binding activity. PG - 152217 LID - S0171-2985(22)00043-2 [pii] LID - 10.1016/j.imbio.2022.152217 [doi] AB - Considering the important role of Der f 2 in house dust mites mediating allergic diseases and allergic adverse effects during allergen-specific immunotherapy (AIT), we intend to develop a candidate of desensitization vaccines against Der f 2 without allergenicity. According to the reported immunoglobulin E (IgE)-binding B and T cell epitopes of Der f 2, four candidates of desensitization vaccines against Der f 2 were developed. Recombinant wild-type Der f 2 (rWt-Der f 2) preserved conformational and linear IgE-binding B epitopes. rWt-Der f 2 linearized by reduction and alkylation reactions (rWt-Der f 2 (red/alk)) and recombinant modified-type Der f 2 (rMt-Der f 2) were developed via destroying conformational and linear IgE-binding B epitopes respectively. rMt-Der f 2 linearized by reduction and alkylation reactions (rMt-Der f 2 (red/alk)) was developed by destroying conformational and linear IgE-binding B epitopes. T cell epitopes of 4 candidates were preserved. The change of their IgE-binding activity was determined by enzyme linked immunosorbent assay (ELISA), western blot and inhibition ELISA. Compared with rWt-Der f 2, the IgE-binding activity of rWt-Der f 2 (red/alk), rMt-Der f 2 and rMt-Der f 2 (red/alk) all decreased, which was consistent with the result of western blot. The IgE-binding activity of rMt-Der f 2 and rMt-Der f 2 (red/alk) was not significantly different (P = 0.0863 > 0.05), which was comparable to that of their corresponding negative controls (P = 0.3488 and 0.4459, both > 0.05). The result of inhibition ELISA also showed that their IgE-binding activity decreased, and rMt-Der f 2 (red/alk) was the lowest. Conclusively, we developed the candidate of desensitization vaccines against Der f 2, rMt-Der f 2 or rMt-Der f 2 (red/alk), nearly without allergenicity, which would potentially prevent HDM allergic patients from allergic adverse effects caused by AIT. CI - Copyright (c) 2022. Published by Elsevier GmbH. FAU - Ling, Xiao-Jing AU - Ling XJ AD - Precision Medicine Center, The First Affiliated Hospital of Gannan Medical University, Ganzhou, China; Department of Clinical Pharmacy, School of Pharmacy, Nanjing Medical University, Nanjing, China; Clinical Allergy Center, The First Affiliated Hospital of Nanjing Medical University, Nanjing, China. FAU - Pan, Chen AU - Pan C AD - School of Basic Medicine and Clinical Pharmacy, China Pharmaceutical University, Nanjing, China. FAU - Tan, Ling-Xiao AU - Tan LX AD - Department of Respiratory Medicine, Children's Hospital of Nanjing Medical University, Nanjing, China. FAU - Zhu, Ying AU - Zhu Y AD - Department of Blood Transfusion, The First Affiliated Hospital of Gannan Medical University, Ganzhou, China. FAU - Yang, Yu-Xing AU - Yang YX AD - Precision Medicine Center, The First Affiliated Hospital of Gannan Medical University, Ganzhou, China. FAU - Zeng, Xiao-Fei AU - Zeng XF AD - Precision Medicine Center, The First Affiliated Hospital of Gannan Medical University, Ganzhou, China. FAU - Sun, Jin-Lyu AU - Sun JL AD - Department of Allergy, State Key Laboratory of Complex Severe and Rare Diseases, Peking Union Medical College Hospital, Chinese Academy of Medical Science and Peking Union Medical College, Beijing, China. Electronic address: sunjinlv@pumch.cn. FAU - Wei, Ji-Fu AU - Wei JF AD - Department of Pharmacy, Jiangsu Cancer Hospital & Jiangsu Institute of Cancer Research & The Affiliated Cancer Hospital of Nanjing Medical University, Nanjing, China; Department of Clinical Pharmacy, School of Pharmacy, Nanjing Medical University, Nanjing, China; Clinical Allergy Center, The First Affiliated Hospital of Nanjing Medical University, Nanjing, China. Electronic address: weijifu@njmu.edu.cn. FAU - Lu, Chen AU - Lu C AD - Precision Medicine Center, The First Affiliated Hospital of Gannan Medical University, Ganzhou, China. Electronic address: gzfylc@163.com. LA - eng PT - Journal Article PT - Research Support, Non-U.S. Gov't DEP - 20220412 PL - Netherlands TA - Immunobiology JT - Immunobiology JID - 8002742 RN - 0 (Allergens) RN - 0 (Antigens, Dermatophagoides) RN - 0 (Arthropod Proteins) RN - 0 (Dermatophagoides farinae antigen f 2) RN - 0 (Epitopes, T-Lymphocyte) RN - 0 (Vaccines) RN - 37341-29-0 (Immunoglobulin E) RN - EC 2.7.10.1 (Receptor Protein-Tyrosine Kinases) SB - IM MH - Allergens MH - Antigens, Dermatophagoides MH - Arthropod Proteins MH - Epitopes, T-Lymphocyte MH - Humans MH - *Hypersensitivity/prevention & control MH - Immunoglobulin E MH - Receptor Protein-Tyrosine Kinases MH - *Vaccines OTO - NOTNLM OT - Conformational IgE-binding B epitopes OT - Der f 2 OT - Desensitization vaccines OT - Linear IgE-binding B epitopes EDAT- 2022/05/18 06:00 MHDA- 2022/06/09 06:00 CRDT- 2022/05/17 18:19 PHST- 2022/02/01 00:00 [received] PHST- 2022/04/09 00:00 [revised] PHST- 2022/04/09 00:00 [accepted] PHST- 2022/05/18 06:00 [pubmed] PHST- 2022/06/09 06:00 [medline] PHST- 2022/05/17 18:19 [entrez] AID - S0171-2985(22)00043-2 [pii] AID - 10.1016/j.imbio.2022.152217 [doi] PST - ppublish SO - Immunobiology. 2022 May;227(3):152217. doi: 10.1016/j.imbio.2022.152217. Epub 2022 Apr 12.