tetano
Editor, Senior Moderator
Sci Adv
. 2022 Dec 23;8(51):eabq3500.
doi: 10.1126/sciadv.abq3500. Epub 2022 Dec 23.
Manganese-coordinated mRNA vaccines with enhanced mRNA expression and immunogenicity induce robust immune responses against SARS-CoV-2 variants
Na Fan[SUP] 1 [/SUP], Kepan Chen[SUP] 1 [/SUP], Rong Zhu[SUP] 2 [/SUP], Zhongwei Zhang[SUP] 1 [/SUP], Hai Huang[SUP] 1 [/SUP], Shugang Qin[SUP] 1 [/SUP], Qian Zheng[SUP] 1 [/SUP], Zhongshan He[SUP] 1 [/SUP], Xi He[SUP] 1 [/SUP], Wen Xiao[SUP] 1 [/SUP], Yupei Zhang[SUP] 1 [/SUP], Yongjun Gu[SUP] 1 [/SUP], Changchun Zhao[SUP] 1 [/SUP], Yongmei Liu[SUP] 1 [/SUP], Xin Jiang[SUP] 1 [/SUP], Shuaicheng Li[SUP] 3 [/SUP], Yuquan Wei[SUP] 1 [/SUP], Xiangrong Song[SUP] 1 [/SUP]
Affiliations
Abstract
It is urgent to develop more effective mRNA vaccines against the emerging severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) variants owing to the immune escape. Here, we constructed a novel mRNA delivery system [IC8/Mn lipid nanoparticles (IC8/Mn LNPs)]with high immunogenicity, via introducing a stimulator of interferon genes (STING) agonist [manganese (Mn)] based on a newly synthesized ionizable lipid (IC8). It was found that Mn can not only promote maturation of antigen-presenting cells via activating STING pathway but also improve mRNA expression by facilitating lysosomal escape for the first time. Subsequently, IC8/Mn LNPs loaded with mRNA encoding the Spike protein of SARS-CoV-2 Delta or Omicron variant (IC8/Mn@D or IC8/Mn@O) were prepared. Both mRNA vaccines induced substantial specific immunoglobulin G responses against Delta or Omicron. IC8/Mn@D displayed strong pseudovirus neutralization ability, T helper 1-biased immune responses, and good safety. It can be concluded that IC8/Mn LNPs have great potential for developing Mn-coordinated mRNA vaccines with robust immunogenicity and good safety.
. 2022 Dec 23;8(51):eabq3500.
doi: 10.1126/sciadv.abq3500. Epub 2022 Dec 23.
Manganese-coordinated mRNA vaccines with enhanced mRNA expression and immunogenicity induce robust immune responses against SARS-CoV-2 variants
Na Fan[SUP] 1 [/SUP], Kepan Chen[SUP] 1 [/SUP], Rong Zhu[SUP] 2 [/SUP], Zhongwei Zhang[SUP] 1 [/SUP], Hai Huang[SUP] 1 [/SUP], Shugang Qin[SUP] 1 [/SUP], Qian Zheng[SUP] 1 [/SUP], Zhongshan He[SUP] 1 [/SUP], Xi He[SUP] 1 [/SUP], Wen Xiao[SUP] 1 [/SUP], Yupei Zhang[SUP] 1 [/SUP], Yongjun Gu[SUP] 1 [/SUP], Changchun Zhao[SUP] 1 [/SUP], Yongmei Liu[SUP] 1 [/SUP], Xin Jiang[SUP] 1 [/SUP], Shuaicheng Li[SUP] 3 [/SUP], Yuquan Wei[SUP] 1 [/SUP], Xiangrong Song[SUP] 1 [/SUP]
Affiliations
- PMID: 36563159
- DOI: 10.1126/sciadv.abq3500
Abstract
It is urgent to develop more effective mRNA vaccines against the emerging severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) variants owing to the immune escape. Here, we constructed a novel mRNA delivery system [IC8/Mn lipid nanoparticles (IC8/Mn LNPs)]with high immunogenicity, via introducing a stimulator of interferon genes (STING) agonist [manganese (Mn)] based on a newly synthesized ionizable lipid (IC8). It was found that Mn can not only promote maturation of antigen-presenting cells via activating STING pathway but also improve mRNA expression by facilitating lysosomal escape for the first time. Subsequently, IC8/Mn LNPs loaded with mRNA encoding the Spike protein of SARS-CoV-2 Delta or Omicron variant (IC8/Mn@D or IC8/Mn@O) were prepared. Both mRNA vaccines induced substantial specific immunoglobulin G responses against Delta or Omicron. IC8/Mn@D displayed strong pseudovirus neutralization ability, T helper 1-biased immune responses, and good safety. It can be concluded that IC8/Mn LNPs have great potential for developing Mn-coordinated mRNA vaccines with robust immunogenicity and good safety.