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We previously developed a lipopolyplex (LPP)\u2010based mRNA vaccine (SW0123) that demonstrated robust immunogenicity and strong protective capacity against severe acute respiratory syndrome coronavirus\u20102 (SARS\u2010CoV\u20102) infection in mice and rhesus macaques. However, the immune profiles and mechanisms of pulmonary protection induced by SW0123 remain unclear. Through high\u2010resolution single\u2010cell analysis, we found that SW0123 vaccination effectively suppressed SARS\u2010CoV\u20102\u2010induced inflammatory responses by inhibiting the recruitment of proinflammatory macrophages and increasing the frequency of polymorphonuclear myeloid\u2010derived 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\u2010induced lung protection. Cell\u2212cell 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\u2010CoV\u20102 infection.<\/jats:p>","DOI":"10.1002\/jmv.28161","type":"journal-article","created":{"date-parts":[[2022,9,20]],"date-time":"2022-09-20T02:09:44Z","timestamp":1663639784000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":7,"title":["Single\u2010cell transcriptome atlas reveals protective characteristics of COVID\u201019 mRNA vaccine"],"prefix":"10.1002","volume":"95","author":[{"given":"Yong","family":"Tan","sequence":"first","affiliation":[{"name":"Research Center for Translational Medicine, Shanghai East Hospital Tongji University School of Medicine  Shanghai China"},{"name":"Department of Liver Surgery, Shanghai Institute of Transplantation Renji Hospital, Shanghai Jiao Tong University School of Medicine  Shanghai 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