A core-shell structured COVID-19 mRNA vaccine with favorable biodistribution pattern and promising immunity

Ren Yang,Xiaopin Ma,Li Zhao,Yujian Zhang,Jincun Zhao,Yuhua Li,Wen Wang,Hangwen Li,Baoying Huang,Zhongmin Liu,Ruhan A,Luyao Zhang,Zhenlin Zhan ,Ang Lin,Peihua Niu,Yufei Wang,Weiguo Yao,Lei Huang,Yao Deng,Shiqiang Li,Wenling Wang,Xiaozhong Peng,Jingjing Liu,Shuaiyao Lu,Xing‐Jie Liang ,Wenjie Tan

doi:10.1038/s41392-021-00634-z

Abstract

Although inoculation of COVID-19 vaccines has rolled out globally, there is still a critical need for safe and effective vaccines to ensure fair and equitable supply for all countries. Here, we report on the development of a highly efficacious mRNA vaccine, SW0123 that is composed of sequence-modified mRNA encoding the full-length SARS-CoV-2 Spike protein packaged in core–shell structured lipopolyplex (LPP) nanoparticles. SW0123 is easy to produce using a large-scale microfluidics-based apparatus. The unique core–shell structured nanoparticle facilitates vaccine uptake and demonstrates a high colloidal stability, and a desirable biodistribution pattern with low liver targeting effect upon intramuscular administration. Extensive evaluations in mice and nonhuman primates revealed strong immunogenicity of SW0123, represented by induction of Th1-polarized T cell responses and high levels of antibodies that were capable of neutralizing not only the wild-type SARS-CoV-2, but also a panel of variants including D614G and N501Y variants. In addition, SW0123 conferred effective protection in both mice and non-human primates upon SARS-CoV-2 challenge. Taken together, SW0123 is a promising vaccine candidate that holds prospects for further evaluation in humans.

Highlights

INTRODUCTION Since the outbreak ofCOVID-19, a large number of vaccine programs have been initiated using a variety of SARS-CoV-2 antigen and vaccine modalities such as live-attenuated virus, inactivated virus, viral protein-expressing adenovirus, recombinant viral protein, and nucleic acid (DNA and mRNA) vaccines encoding either full-length or partial viral antigen.[1]
13 weeks with no significant decline as compared with that these results demonstrate that SW0123 conferred highly effective measured at week 5, which is in line with the sustained Ab protection against SARS-CoV-2 infection in Rhesus macaques (RMs)
As the key component in the vaccine formulation, LPP is endowed with multiple advantages including superior colloidal stability, high encapsulation and delivery efficiency, as well as desirable biodistribution pattern

Summary

Introduction

INTRODUCTION Since the outbreak ofCOVID-19, a large number of vaccine programs have been initiated using a variety of SARS-CoV-2 antigen and vaccine modalities such as live-attenuated virus, inactivated virus, viral protein-expressing adenovirus, recombinant viral protein, and nucleic acid (DNA and mRNA) vaccines encoding either full-length or partial viral antigen.[1]. It is becoming increasingly evident that an effective vaccine needs to elicit durable responses due to rapid waning immunity observed in COVID-19 patients,[8,9] and in the meantime provides protection against emerging SARS-CoV-2 variants with increased infectivity and transmissibility such as the D614G variant.[10] A fundamental understanding of the immune mechanisms associated with broad protection is critical to guide the ongoing COVID-19 vaccine development. A number of COVID-19 mRNA candidate vaccines had been successfully developed shortly after the genomic sequence of SARS-CoV-2 was identified.[5,7] Some of these vaccines were the first to enter clinical trials and have been licensed by FDA.[14]

Methods

Findings

Conclusion