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Variant-specific vaccination induces systems immune responses and potent in vivo protection against SARS-CoV-2.
Peng, Lei; Renauer, Paul A; Ökten, Arya; Fang, Zhenhao; Park, Jonathan J; Zhou, Xiaoyu; Lin, Qianqian; Dong, Matthew B; Filler, Renata; Xiong, Qiancheng; Clark, Paul; Lin, Chenxiang; Wilen, Craig B; Chen, Sidi.
  • Peng L; Department of Genetics, Yale University School of Medicine, New Haven, CT, USA; System Biology Institute, Yale University, West Haven, CT, USA; Center for Cancer Systems Biology, Yale University, West Haven, CT, USA.
  • Renauer PA; Department of Genetics, Yale University School of Medicine, New Haven, CT, USA; System Biology Institute, Yale University, West Haven, CT, USA; Center for Cancer Systems Biology, Yale University, West Haven, CT, USA; Molecular Cell Biology, Genetics, and Development Program, Yale University, New Hav
  • Ökten A; Department of Immunobiology, Yale University, New Haven, CT, USA; Department of Laboratory Medicine, Yale University, New Haven, CT, USA.
  • Fang Z; Department of Genetics, Yale University School of Medicine, New Haven, CT, USA; System Biology Institute, Yale University, West Haven, CT, USA; Center for Cancer Systems Biology, Yale University, West Haven, CT, USA.
  • Park JJ; Department of Genetics, Yale University School of Medicine, New Haven, CT, USA; System Biology Institute, Yale University, West Haven, CT, USA; Center for Cancer Systems Biology, Yale University, West Haven, CT, USA; M.D.-Ph.D. Program, Yale University, West Haven, CT, USA.
  • Zhou X; Department of Genetics, Yale University School of Medicine, New Haven, CT, USA; System Biology Institute, Yale University, West Haven, CT, USA; Center for Cancer Systems Biology, Yale University, West Haven, CT, USA.
  • Lin Q; Department of Genetics, Yale University School of Medicine, New Haven, CT, USA; System Biology Institute, Yale University, West Haven, CT, USA; Center for Cancer Systems Biology, Yale University, West Haven, CT, USA.
  • Dong MB; Department of Genetics, Yale University School of Medicine, New Haven, CT, USA; System Biology Institute, Yale University, West Haven, CT, USA; Center for Cancer Systems Biology, Yale University, West Haven, CT, USA; Department of Immunobiology, Yale University, New Haven, CT, USA; M.D.-Ph.D. Progra
  • Filler R; Department of Immunobiology, Yale University, New Haven, CT, USA; Department of Laboratory Medicine, Yale University, New Haven, CT, USA.
  • Xiong Q; Department of Cell Biology, Yale University, New Haven, CT, USA; Nanobiology Institute, Yale University, New Haven, CT, USA.
  • Clark P; Department of Genetics, Yale University School of Medicine, New Haven, CT, USA; System Biology Institute, Yale University, West Haven, CT, USA; Center for Cancer Systems Biology, Yale University, West Haven, CT, USA.
  • Lin C; Department of Cell Biology, Yale University, New Haven, CT, USA; Department of Biomedical Engineering, Yale University, New Haven, CT, USA; Nanobiology Institute, Yale University, New Haven, CT, USA.
  • Wilen CB; Department of Immunobiology, Yale University, New Haven, CT, USA; Department of Laboratory Medicine, Yale University, New Haven, CT, USA. Electronic address: craig.wilen@yale.edu.
  • Chen S; Department of Genetics, Yale University School of Medicine, New Haven, CT, USA; System Biology Institute, Yale University, West Haven, CT, USA; Center for Cancer Systems Biology, Yale University, West Haven, CT, USA; Molecular Cell Biology, Genetics, and Development Program, Yale University, New Hav
Cell Rep Med ; 3(5): 100634, 2022 05 17.
Article in English | MEDLINE | ID: covidwho-1805326
ABSTRACT
Lipid nanoparticle (LNP)-mRNA vaccines offer protection against COVID-19; however, multiple variant lineages caused widespread breakthrough infections. Here, we generate LNP-mRNAs specifically encoding wild-type (WT), B.1.351, and B.1.617 SARS-CoV-2 spikes, and systematically study their immune responses. All three LNP-mRNAs induced potent antibody and T cell responses in animal models; however, differences in neutralization activity have been observed between variants. All three vaccines offer potent protection against in vivo challenges of authentic viruses of WA-1, Beta, and Delta variants. Single-cell transcriptomics of WT- and variant-specific LNP-mRNA-vaccinated animals reveal a systematic landscape of immune cell populations and global gene expression. Variant-specific vaccination induces a systemic increase of reactive CD8 T cells and altered gene expression programs in B and T lymphocytes. BCR-seq and TCR-seq unveil repertoire diversity and clonal expansions in vaccinated animals. These data provide assessment of efficacy and direct systems immune profiling of variant-specific LNP-mRNA vaccination in vivo.
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Full text: Available Collection: International databases Database: MEDLINE Main subject: SARS-CoV-2 / COVID-19 Type of study: Systematic review/Meta Analysis Topics: Vaccines / Variants Limits: Animals / Humans Language: English Journal: Cell Rep Med Year: 2022 Document Type: Article Affiliation country: J.xcrm.2022.100634

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Full text: Available Collection: International databases Database: MEDLINE Main subject: SARS-CoV-2 / COVID-19 Type of study: Systematic review/Meta Analysis Topics: Vaccines / Variants Limits: Animals / Humans Language: English Journal: Cell Rep Med Year: 2022 Document Type: Article Affiliation country: J.xcrm.2022.100634