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Chimeric spike mRNA vaccines protect against Sarbecovirus challenge in mice.
Martinez, David R; Schäfer, Alexandra; Leist, Sarah R; De la Cruz, Gabriela; West, Ande; Atochina-Vasserman, Elena N; Lindesmith, Lisa C; Pardi, Norbert; Parks, Robert; Barr, Maggie; Li, Dapeng; Yount, Boyd; Saunders, Kevin O; Weissman, Drew; Haynes, Barton F; Montgomery, Stephanie A; Baric, Ralph S.
  • Martinez DR; Department of Epidemiology, University of North Carolina at Chapel Hill, Chapel Hill, NC, USA. david.rafael.martinez@gmail.com rbaric@email.unc.edu.
  • Schäfer A; Department of Epidemiology, University of North Carolina at Chapel Hill, Chapel Hill, NC, USA.
  • Leist SR; Department of Epidemiology, University of North Carolina at Chapel Hill, Chapel Hill, NC, USA.
  • De la Cruz G; Lineberger Comprehensive Cancer Center, University of North Carolina School of Medicine, Chapel Hill, NC, USA.
  • West A; Department of Epidemiology, University of North Carolina at Chapel Hill, Chapel Hill, NC, USA.
  • Atochina-Vasserman EN; Infectious Disease Division, Department of Medicine, Perelman School of Medicine, University of Pennsylvania Perelman School of Medicine, Philadelphia, PA, USA.
  • Lindesmith LC; Department of Epidemiology, University of North Carolina at Chapel Hill, Chapel Hill, NC, USA.
  • Pardi N; Infectious Disease Division, Department of Medicine, Perelman School of Medicine, University of Pennsylvania Perelman School of Medicine, Philadelphia, PA, USA.
  • Parks R; Duke Human Vaccine Institute, Duke University School of Medicine, Durham, NC, USA.
  • Barr M; Duke Human Vaccine Institute, Duke University School of Medicine, Durham, NC, USA.
  • Li D; Duke Human Vaccine Institute, Duke University School of Medicine, Durham, NC, USA.
  • Yount B; Department of Epidemiology, University of North Carolina at Chapel Hill, Chapel Hill, NC, USA.
  • Saunders KO; Duke Human Vaccine Institute, Duke University School of Medicine, Durham, NC, USA.
  • Weissman D; Infectious Disease Division, Department of Medicine, Perelman School of Medicine, University of Pennsylvania Perelman School of Medicine, Philadelphia, PA, USA.
  • Haynes BF; Duke Human Vaccine Institute, Duke University School of Medicine, Durham, NC, USA.
  • Montgomery SA; Department of Laboratory Medicine and Pathology, University of North Carolina School of Medicine, Chapel Hill, NC, USA.
  • Baric RS; Department of Epidemiology, University of North Carolina at Chapel Hill, Chapel Hill, NC, USA. david.rafael.martinez@gmail.com rbaric@email.unc.edu.
Science ; 373(6558): 991-998, 2021 08 27.
Article in English | MEDLINE | ID: covidwho-1295160
ABSTRACT
The emergence of severe acute respiratory syndrome coronavirus (SARS-CoV) in 2003 and SARS-CoV-2 in 2019 highlights the need to develop universal vaccination strategies against the broader Sarbecovirus subgenus. Using chimeric spike designs, we demonstrate protection against challenge from SARS-CoV, SARS-CoV-2, SARS-CoV-2 B.1.351, bat CoV (Bt-CoV) RsSHC014, and a heterologous Bt-CoV WIV-1 in vulnerable aged mice. Chimeric spike messenger RNAs (mRNAs) induced high levels of broadly protective neutralizing antibodies against high-risk Sarbecoviruses. By contrast, SARS-CoV-2 mRNA vaccination not only showed a marked reduction in neutralizing titers against heterologous Sarbecoviruses, but SARS-CoV and WIV-1 challenge in mice resulted in breakthrough infections. Chimeric spike mRNA vaccines efficiently neutralized D614G, mink cluster five, and the UK B.1.1.7 and South African B.1.351 variants of concern. Thus, multiplexed-chimeric spikes can prevent SARS-like zoonotic coronavirus infections with pandemic potential.
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Full text: Available Collection: International databases Database: MEDLINE Main subject: Viral Vaccines / Vaccines, Synthetic / Coronavirus Infections / Spike Glycoprotein, Coronavirus / Betacoronavirus / COVID-19 Vaccines Type of study: Prognostic study / Randomized controlled trials Topics: Vaccines / Variants Limits: Animals Language: English Journal: Science Year: 2021 Document Type: Article

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Full text: Available Collection: International databases Database: MEDLINE Main subject: Viral Vaccines / Vaccines, Synthetic / Coronavirus Infections / Spike Glycoprotein, Coronavirus / Betacoronavirus / COVID-19 Vaccines Type of study: Prognostic study / Randomized controlled trials Topics: Vaccines / Variants Limits: Animals Language: English Journal: Science Year: 2021 Document Type: Article