Author: Wang, Bo ; Duan, Xuewen ; Lu, Shuaiyao ; Lin, Ang ; Peng, Xiaozhong ; Li, Hangwen ; Zhang, Yunkai ; Liu, Xingguang ; Zhan, Zhenzhen ; Tan, Yong

AbstractMessenger RNA (mRNA) vaccines are promising alternatives to conventional vaccines in many aspects. We previously developed a lipopolyplex (LPP)‐based mRNA vaccine (SW0123) that demonstrated robust immunogenicity and strong protective capacity against severe acute respiratory syndrome coronavirus‐2 (SARS‐CoV‐2) infection in mice and rhesus macaques. However, the immune profiles and mechanisms of pulmonary protection induced by SW0123 remain unclear. Through high‐resolution single‐cell analysis, we found that SW0123 vaccination effectively suppressed SARS‐CoV‐2‐induced inflammatory responses by inhibiting the recruitment of proinflammatory macrophages and increasing the frequency of polymorphonuclear myeloid‐derived suppressor cells. In addition, the apoptotic process in both lung epithelial and endothelial cells was significantly inhibited, which was proposed to be one major mechanism contributing to vaccine‐induced lung protection. Cell−cell interaction in the lung compartment was also altered by vaccination. These data collectively unravel the mechanisms by which the SW0123 protects against lung damage caused by SARS‐CoV‐2 infection.

Signal Transduction and Targeted TherapyQ1 · MEDICINE

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

Q1 · MEDICINE

ArticleOA

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

AbstractAlthough 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.

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Indication	Highest Phase	Country/Location	Organization	Date
COVID-19	Phase 2	CN	Stemirna Therapeutics Co., Ltd.Startup	06 Jun 2022

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