Lipid nanoparticle-encapsulated mRNA antibody provides long-term protection against SARS-CoV-2 in mice and hamsters

Xiaojing Zhang ,Tiecheng Wang ,Liangzhi Xie ,Shunqing Xu ,Nana Zhang ,Hang Chi,Cheng‐Feng Qin ,Tian-Shu Cao,Yong‐Qiang Deng ,Qing Ye,Yuwei Gao ,Chunjian Qi ,Shulong Zu ,Hong-Ying Qiu,Xianghui Duan ,Bo Ying,Hui Zhao,Yifei Zhang ,Dandan Lin ,Chao Zhou,X.y. Zhong

doi:10.1038/s41422-022-00630-0

Abstract

Monoclonal antibodies represent important weapons in our arsenal to against the COVID-19 pandemic. However, this potential is severely limited by the time-consuming process of developing effective antibodies and the relative high cost of manufacturing. Herein, we present a rapid and cost-effective lipid nanoparticle (LNP) encapsulated-mRNA platform for in vivo delivery of SARS-CoV-2 neutralization antibodies. Two mRNAs encoding the light and heavy chains of a potent SARS-CoV-2 neutralizing antibody HB27, which is currently being evaluated in clinical trials, were encapsulated into clinical grade LNP formulations (named as mRNA-HB27-LNP). In vivo characterization demonstrated that intravenous administration of mRNA-HB27-LNP in mice resulted in a longer circulating half-life compared with the original HB27 antibody in protein format. More importantly, a single prophylactic administration of mRNA-HB27-LNP provided protection against SARS-CoV-2 challenge in mice at 1, 7 and even 63 days post administration. In a close contact transmission model, prophylactic administration of mRNA-HB27-LNP prevented SARS-CoV-2 infection between hamsters in a dose-dependent manner. Overall, our results demonstrate a superior long-term protection against SARS-CoV-2 conferred by a single administration of this unique mRNA antibody, highlighting the potential of this universal platform for antibody-based disease prevention and therapy against COVID-19 as well as a variety of other infectious diseases.

Highlights

Coronavirus disease 2019 (COVID-19) caused by the newly identified severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), has resulted in a public health crisis worldwide.[1]
In vitro and in vivo characterization of mRNA-HB27-lipid nanoparticle (LNP) Recently, we have developed a potent SARS-CoV-2 neutralizing human monoclonal antibodies (mAbs) HB27, which targets the receptor binding domain (RBD) of spike (S) protein,[15] and the therapeutic efficacy against mild or moderated COVID-19 patients are being evaluated in phase II clinical trials (NCT04644185)
The feasibility of in vivo delivery of antibody based on the mRNALNP platform has been well demonstrated in recent years, and a dozen of mRNA-encoding mAbs are advancing to clinical trials for prophylactic or therapeutic purpose against infectious diseases or cancers

Summary

Introduction

Coronavirus disease 2019 (COVID-19) caused by the newly identified severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), has resulted in a public health crisis worldwide.[1]. As of January 3, 2022, there are 290,439,443 confirmed cases and 5,459,800 deaths worldwide, with 220 countries/regions affected (https://coronavirus.jhu.edu/map.html). Global efforts are ongoing to treat COVID-19 and to flatten the pandemic curve. Several vaccines, including inactivated vaccine, recombinant protein, adenovirus vector, and mRNA vaccine have been approved for the prevention and control of pandemic.[2]. Only a few antiviral drugs have shown therapeutic effect in clinical trials,[3] and the development of safe and effective countermeasures remains of high priority. While vaccination represents the best strategy to prevent

Methods

Results

Conclusion