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Intranasal delivery of replicating mRNA encoding hACE2-targeting antibody against SARS-CoV-2 Omicron infection in the hamster

Intranasal delivery of replicating mRNA encoding hACE2-targeting antibody against SARS-CoV-2 Omicron infection in the hamster

Authors :
Ya-Nan Zhang
Hong-Qing Zhang
Gui-Feng Wang
Zhe-Rui Zhang
Jia-Qi Li
Xiao-Ling Chen
Yan-Yan Hu
Xiang-Yue Zeng
Yu-Jia Shi
Jing Wang
Ying-Hua Li
Xiao-Dan Li
Chun-He Wang
Bing Zhu
Bo Zhang
Source :
Antiviral research. 209
Publication Year :
2022

Abstract

The Omicron variant is sweeping the world, which displays striking immune escape potential through mutations at key antigenic sites on the spike protein, making broad-spectrum SARS-CoV-2 prevention or therapeutical strategies urgently needed. Previously, we have reported a hACE2-targeting neutralizing antibody 3E8, which could efficiently block both prototype SARS-CoV-2 and Delta variant infections in prophylactic mouse models, having the potential of broad-spectrum to prevent SARS-CoV-2. However, preparation of monoclonal neutralizing antibodies is severely limited by the time-consuming process and the relative high cost. Here, we utilized a modified VEEV replicon with two subgenomic (sg) promoters engineered to express the light and heavy chains of the 3E8 mAb. The feasibility and protective efficacy of replicating mRNA encoding 3E8 against Omicron infection in the hamster were demonstrated through the lung targeting delivery with the help of VEEV-VRP. Overall, we developed a safe and cost-effective platform of broad-spectrum to prevent SARS-CoV-2 infection.

Subjects

Subjects :
Pharmacology
Virology

Details

ISSN :
18729096
Volume :
209
Database :
OpenAIRE
Journal :
Antiviral research
Accession number :
edsair.doi.dedup.....02c2ab16be573c4e8a8ad1d7877ce8d5