Intranasal delivery of replicating mRNA encoding neutralizing antibody against SARS-CoV-2 infection in mice
| Autor: | Jia-Qi Li, Ya-Nan Zhang, Bo Zhang, Cheng-Lin Deng, Qiu-Yan Zhang, Xiao-Dan Li, Hong-Qing Zhang, Zhe-Rui Zhang, Xiang-Yue Zeng, Han-Qing Ye |
|---|---|
| Rok vydání: | 2021 |
| Předmět: |
Cancer Research
QH301-705.5 Molecular biology viruses Alphavirus Antibodies Viral Microbiology Article Mice In vivo Cricetinae Chlorocebus aethiops Genetics Animals RNA Messenger Replicon Biology (General) Neutralizing antibody Vero Cells Subgenomic mRNA Mice Inbred BALB C biology SARS-CoV-2 COVID-19 biochemical phenomena metabolism and nutrition respiratory system biology.organism_classification Antibodies Neutralizing Virology respiratory tract diseases Titer biology.protein Vero cell Medicine Female Antibody |
| Zdroj: | Signal Transduction and Targeted Therapy Signal Transduction and Targeted Therapy, Vol 6, Iss 1, Pp 1-8 (2021) |
| ISSN: | 2059-3635 |
| Popis: | The lung is the prophylaxis target against SARS-CoV-2 infection, and neutralizing antibodies are a leading class of biological products against various infectious viral pathogen. In this study, we develop a safe and cost-effective platform to express neutralizing antibody in the lung with replicating mRNA basing on alphavirus replicon particle (VRP) delivery system, to prevent SARS-CoV-2 infections. First, a modified VEEV replicon with two subgenomic (sg) promoters was engineered to translate the light and heavy chains of antibody simultaneously, for expression and assembly of neutralizing anti-SARS-CoV-2 antibody CB6. Second, the feasibility and protective efficacy of replicating mRNA against SARS-CoV-2 infection were demonstrated through both in vitro and in vivo assays. The lung target delivery with the help of VRP system resulted in efficiently block SARS-CoV-2 infection with reducing viral titer and less tissue damage in the lung of mice. Overall, our data suggests that expressing neutralizing antibodies in the lungs with the help of self-replicating mRNA could potentially be a promising prophylaxis approach against SARS-CoV-2 infection. |
| Databáze: | OpenAIRE |
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