Design and evaluation of mRNA encoding recombinant neutralizing antibodies for botulinum neurotoxin type B intoxication prophylaxis
Among all natural and synthetic toxins, botulinum neurotoxins (BoNTs), produced by Clostridium botulinum in an anaerobic environment, are the most toxic polymer proteins. Currently, the most effective modalities for botulism prevention and treatment are vaccination and antitoxin use, respectively. H...
Saved in:
| Main Authors: | , , , , , , , , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
Taylor & Francis Group
2024-12-01
|
| Series: | Human Vaccines & Immunotherapeutics |
| Subjects: | |
| Online Access: | https://www.tandfonline.com/doi/10.1080/21645515.2024.2358570 |
| Tags: |
Add Tag
No Tags, Be the first to tag this record!
|
| _version_ | 1849744202322149376 |
|---|---|
| author | Gulisaina Qiaerxie Yujia Jiang Gege Li Zhixin Yang Feng Long Yunzhou Yu Jian Sheng Lu Peng Du Yong Cui |
| author_facet | Gulisaina Qiaerxie Yujia Jiang Gege Li Zhixin Yang Feng Long Yunzhou Yu Jian Sheng Lu Peng Du Yong Cui |
| author_sort | Gulisaina Qiaerxie |
| collection | DOAJ |
| description | Among all natural and synthetic toxins, botulinum neurotoxins (BoNTs), produced by Clostridium botulinum in an anaerobic environment, are the most toxic polymer proteins. Currently, the most effective modalities for botulism prevention and treatment are vaccination and antitoxin use, respectively. However, these modalities are associated with long response time for active immunization, side effects, and donor limitations. As such, the development of more promising botulism prevention and treatment modalities is warranted. Here, we designed an mRNA encoding B9-hFc – a heavy-chain antibody fused to VHH and human Fc that can neutralize BoNT serotype B (BoNT/B) effectively – and assessed its expression in vitro and in vivo. The results confirmed that our mRNA demonstrates good expression in vitro and in vivo. Moreover, a single mRNA lipid nanoparticle injection effectively prevents BoNT/B intoxication in vivo, with effects comparable to those of protein antibodies. In conclusion, we explored and clarified whether mRNA drugs encoding neutralizing antibodies prevent BoNT/B intoxication. Our results provide an efficient strategy for further research on the prevention and treatment of intoxication by botulinum toxin. |
| format | Article |
| id | doaj-art-3b3fe064d75d437cbf9daed028543ef6 |
| institution | DOAJ |
| issn | 2164-5515 2164-554X |
| language | English |
| publishDate | 2024-12-01 |
| publisher | Taylor & Francis Group |
| record_format | Article |
| series | Human Vaccines & Immunotherapeutics |
| spelling | doaj-art-3b3fe064d75d437cbf9daed028543ef62025-08-20T03:21:46ZengTaylor & Francis GroupHuman Vaccines & Immunotherapeutics2164-55152164-554X2024-12-0120110.1080/21645515.2024.2358570Design and evaluation of mRNA encoding recombinant neutralizing antibodies for botulinum neurotoxin type B intoxication prophylaxisGulisaina Qiaerxie0Yujia Jiang1Gege Li2Zhixin Yang3Feng Long4Yunzhou Yu5Jian Sheng Lu6Peng Du7Yong Cui8School of Medical Device, Shenyang Pharmaceutical University, Shenyang, Liaoning, ChinaLaboratory of Advanced Biotechnology, Beijing Institute of Biotechnology, Beijing, ChinaSchool of Medical Device, Shenyang Pharmaceutical University, Shenyang, Liaoning, ChinaLaboratory of Advanced Biotechnology, Beijing Institute of Biotechnology, Beijing, ChinaSchool of Medical Device, Shenyang Pharmaceutical University, Shenyang, Liaoning, ChinaLaboratory of Advanced Biotechnology, Beijing Institute of Biotechnology, Beijing, ChinaLaboratory of Advanced Biotechnology, Beijing Institute of Biotechnology, Beijing, ChinaLaboratory of Advanced Biotechnology, Beijing Institute of Biotechnology, Beijing, ChinaSchool of Medical Device, Shenyang Pharmaceutical University, Shenyang, Liaoning, ChinaAmong all natural and synthetic toxins, botulinum neurotoxins (BoNTs), produced by Clostridium botulinum in an anaerobic environment, are the most toxic polymer proteins. Currently, the most effective modalities for botulism prevention and treatment are vaccination and antitoxin use, respectively. However, these modalities are associated with long response time for active immunization, side effects, and donor limitations. As such, the development of more promising botulism prevention and treatment modalities is warranted. Here, we designed an mRNA encoding B9-hFc – a heavy-chain antibody fused to VHH and human Fc that can neutralize BoNT serotype B (BoNT/B) effectively – and assessed its expression in vitro and in vivo. The results confirmed that our mRNA demonstrates good expression in vitro and in vivo. Moreover, a single mRNA lipid nanoparticle injection effectively prevents BoNT/B intoxication in vivo, with effects comparable to those of protein antibodies. In conclusion, we explored and clarified whether mRNA drugs encoding neutralizing antibodies prevent BoNT/B intoxication. Our results provide an efficient strategy for further research on the prevention and treatment of intoxication by botulinum toxin.https://www.tandfonline.com/doi/10.1080/21645515.2024.2358570Botulinum neurotoxinmRNAprophylaxisheavy-chain antibodylipid nanoparticle |
| spellingShingle | Gulisaina Qiaerxie Yujia Jiang Gege Li Zhixin Yang Feng Long Yunzhou Yu Jian Sheng Lu Peng Du Yong Cui Design and evaluation of mRNA encoding recombinant neutralizing antibodies for botulinum neurotoxin type B intoxication prophylaxis Human Vaccines & Immunotherapeutics Botulinum neurotoxin mRNA prophylaxis heavy-chain antibody lipid nanoparticle |
| title | Design and evaluation of mRNA encoding recombinant neutralizing antibodies for botulinum neurotoxin type B intoxication prophylaxis |
| title_full | Design and evaluation of mRNA encoding recombinant neutralizing antibodies for botulinum neurotoxin type B intoxication prophylaxis |
| title_fullStr | Design and evaluation of mRNA encoding recombinant neutralizing antibodies for botulinum neurotoxin type B intoxication prophylaxis |
| title_full_unstemmed | Design and evaluation of mRNA encoding recombinant neutralizing antibodies for botulinum neurotoxin type B intoxication prophylaxis |
| title_short | Design and evaluation of mRNA encoding recombinant neutralizing antibodies for botulinum neurotoxin type B intoxication prophylaxis |
| title_sort | design and evaluation of mrna encoding recombinant neutralizing antibodies for botulinum neurotoxin type b intoxication prophylaxis |
| topic | Botulinum neurotoxin mRNA prophylaxis heavy-chain antibody lipid nanoparticle |
| url | https://www.tandfonline.com/doi/10.1080/21645515.2024.2358570 |
| work_keys_str_mv | AT gulisainaqiaerxie designandevaluationofmrnaencodingrecombinantneutralizingantibodiesforbotulinumneurotoxintypebintoxicationprophylaxis AT yujiajiang designandevaluationofmrnaencodingrecombinantneutralizingantibodiesforbotulinumneurotoxintypebintoxicationprophylaxis AT gegeli designandevaluationofmrnaencodingrecombinantneutralizingantibodiesforbotulinumneurotoxintypebintoxicationprophylaxis AT zhixinyang designandevaluationofmrnaencodingrecombinantneutralizingantibodiesforbotulinumneurotoxintypebintoxicationprophylaxis AT fenglong designandevaluationofmrnaencodingrecombinantneutralizingantibodiesforbotulinumneurotoxintypebintoxicationprophylaxis AT yunzhouyu designandevaluationofmrnaencodingrecombinantneutralizingantibodiesforbotulinumneurotoxintypebintoxicationprophylaxis AT jianshenglu designandevaluationofmrnaencodingrecombinantneutralizingantibodiesforbotulinumneurotoxintypebintoxicationprophylaxis AT pengdu designandevaluationofmrnaencodingrecombinantneutralizingantibodiesforbotulinumneurotoxintypebintoxicationprophylaxis AT yongcui designandevaluationofmrnaencodingrecombinantneutralizingantibodiesforbotulinumneurotoxintypebintoxicationprophylaxis |