Affiliations
- State Key Laboratory of Pathogen and Biosecurity, Beijing Institute of Microbiology and Epidemiology, AMMS, 100071, Beijing, China.
- College of Life Sciences, Inner Mongolia Agricultural University, Hohhot, 010018, Inner Mongolia, China.
- School of Life Sciences, Henan University, Kaifeng, 475004, Henan, China.
- Suzhou Abogen Biosciences Co., Ltd, Suzhou, 215123, Jiangsu, China.
- State Key Laboratory of Pathogen and Biosecurity, Beijing Institute of Microbiology and Epidemiology, AMMS, 100071, Beijing, China. Electronic address: dengyq1977@126.com.
- State Key Laboratory of Pathogen and Biosecurity, Beijing Institute of Microbiology and Epidemiology, AMMS, 100071, Beijing, China. Electronic address: qincf@bmi.ac.cn.
- Research Unit of Discovery and Tracing of Natural Focus Diseases, Chinese Academy of Medical Sciences, 100071, Beijing, China. Electronic address: qincf@bmi.ac.cn.
PMID: 38531869 PMCID: PMC10966106 DOI: 10.1038/s41392-024-01766-8
Abstract
The Orthopoxvirus genus, especially variola virus (VARV) and monkeypox virus (MPXV), remains a significant public health threat worldwide. The development of therapeutic antibodies against orthopoxviruses is largely hampered by the high cost of antibody engineering and manufacturing processes. mRNA-encoded antibodies have emerged as a powerful and universal platform for rapid antibody production. Herein, by using the established lipid nanoparticle (LNP)-encapsulated mRNA platform, we constructed four mRNA combinations that encode monoclonal antibodies with broad neutralization activities against orthopoxviruses. In vivo characterization demonstrated that a single intravenous injection of each LNP-encapsulated mRNA antibody in mice resulted in the rapid production of neutralizing antibodies. More importantly, mRNA antibody treatments showed significant protection from weight loss and mortality in the vaccinia virus (VACV) lethal challenge mouse model, and a unique mRNA antibody cocktail, Mix2a, exhibited superior in vivo protection by targeting both intracellular mature virus (IMV)-form and extracellular enveloped virus (EEV)-form viruses.
In summary, our results demonstrate the proof-of-concept production of orthopoxvirus antibodies via the LNP-mRNA platform, highlighting the great potential of tailored mRNA antibody combinations as a universal strategy to combat orthopoxvirus as well as other emerging viruses.
