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Variant SARS-CoV-2 mRNA vaccines confer broad neutralization as primary or booster series in mice
Affiliation:1. Moderna, Inc., 200 Technology Square, Cambridge, MA 02139, USA;2. Vaccine Research Center, National Institute of Allergy and Infectious Diseases, National Institutes of Health, 10 Center Dr, Bethesda, MD 20814, USA
Abstract:Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is the causative agent of a global pandemic. Safe and effective COVID-19 vaccines are now available, including mRNA-1273, which has shown 94% efficacy in prevention of symptomatic COVID-19 disease. However, the emergence of SARS-CoV-2 variants has led to concerns of viral escape from vaccine-induced immunity. Several variants have shown decreased susceptibility to neutralization by vaccine-induced immunity, most notably B.1.351 (Beta), although the overall impact on vaccine efficacy remains to be determined. Here, we present the initial evaluation in mice of 2 updated mRNA vaccines designed to target SARS-CoV-2 variants: (1) monovalent mRNA-1273.351 encodes for the spike protein found in B.1.351 and (2) mRNA-1273.211 comprising a 1:1 mix of mRNA-1273 and mRNA-1273.351. Both vaccines were evaluated as a 2-dose primary series in mice; mRNA-1273.351 was also evaluated as a booster dose in animals previously vaccinated with mRNA-1273. The results demonstrated that a primary vaccination series of mRNA-1273.351 was effective at increasing neutralizing antibody titers against B.1.351, while mRNA-1273.211 was effective at providing broad cross-variant neutralization. A third (booster) dose of mRNA-1273.351 significantly increased both wild-type and B.1.351-specific neutralization titers. Both mRNA-1273.351 and mRNA-1273.211 are being evaluated in pre-clinical challenge and clinical studies.
Keywords:COVID-19  SARS-CoV-2 variants of concern  mRNA-1273  Primary series  Booster dose  Neutralization  ACE2"  },{"  #name"  :"  keyword"  ,"  $"  :{"  id"  :"  k0040"  },"  $$"  :[{"  #name"  :"  text"  ,"  _"  :"  angiotensin-converting enzyme 2  ELISA"  },{"  #name"  :"  keyword"  ,"  $"  :{"  id"  :"  k0050"  },"  $$"  :[{"  #name"  :"  text"  ,"  _"  :"  enzyme-linked immunosorbent assay  GMT"  },{"  #name"  :"  keyword"  ,"  $"  :{"  id"  :"  k0060"  },"  $$"  :[{"  #name"  :"  text"  ,"  _"  :"  geometric mean titer  inhibitory dilution factor  IgG"  },{"  #name"  :"  keyword"  ,"  $"  :{"  id"  :"  k0080"  },"  $$"  :[{"  #name"  :"  text"  ,"  _"  :"  immunoglobulin G  LNP"  },{"  #name"  :"  keyword"  ,"  $"  :{"  id"  :"  k0090"  },"  $$"  :[{"  #name"  :"  text"  ,"  _"  :"  lipid nanoparticle  Nab"  },{"  #name"  :"  keyword"  ,"  $"  :{"  id"  :"  k0100"  },"  $$"  :[{"  #name"  :"  text"  ,"  _"  :"  neutralizing antibody  NHPs"  },{"  #name"  :"  keyword"  ,"  $"  :{"  id"  :"  k0110"  },"  $$"  :[{"  #name"  :"  text"  ,"  _"  :"  non-human primates  ns"  },{"  #name"  :"  keyword"  ,"  $"  :{"  id"  :"  k0120"  },"  $$"  :[{"  #name"  :"  text"  ,"  _"  :"  not significant  NTD"  },{"  #name"  :"  keyword"  ,"  $"  :{"  id"  :"  k0130"  },"  $$"  :[{"  #name"  :"  text"  ,"  _"  :"  N-terminal domain  PBS"  },{"  #name"  :"  keyword"  ,"  $"  :{"  id"  :"  k0140"  },"  $$"  :[{"  #name"  :"  text"  ,"  _"  :"  phosphate-buffered saline  PsVN"  },{"  #name"  :"  keyword"  ,"  $"  :{"  id"  :"  k0150"  },"  $$"  :[{"  #name"  :"  text"  ,"  _"  :"  pseudovirus neutralization titer  RBD"  },{"  #name"  :"  keyword"  ,"  $"  :{"  id"  :"  k0160"  },"  $$"  :[{"  #name"  :"  text"  ,"  _"  :"  receptor binding domain  RLUs"  },{"  #name"  :"  keyword"  ,"  $"  :{"  id"  :"  k0170"  },"  $$"  :[{"  #name"  :"  text"  ,"  _"  :"  relative luminescence units  S"  },{"  #name"  :"  keyword"  ,"  $"  :{"  id"  :"  k0180"  },"  $$"  :[{"  #name"  :"  text"  ,"  _"  :"  spike  SARS-CoV-2"  },{"  #name"  :"  keyword"  ,"  $"  :{"  id"  :"  k0190"  },"  $$"  :[{"  #name"  :"  text"  ,"  _"  :"  severe acute respiratory syndrome coronavirus 2  TMB"  },{"  #name"  :"  keyword"  ,"  $"  :{"  id"  :"  k0200"  },"  $$"  :[{"  #name"  :"  text"  ,"  _"  :"  tetramethylbenzidine  UTR"  },{"  #name"  :"  keyword"  ,"  $"  :{"  id"  :"  k0210"  },"  $$"  :[{"  #name"  :"  text"  ,"  _"  :"  untranslated region  VOC"  },{"  #name"  :"  keyword"  ,"  $"  :{"  id"  :"  k0220"  },"  $$"  :[{"  #name"  :"  text"  ,"  _"  :"  variant of concern  VOI"  },{"  #name"  :"  keyword"  ,"  $"  :{"  id"  :"  k0230"  },"  $$"  :[{"  #name"  :"  text"  ,"  _"  :"  variant of interest  VSV"  },{"  #name"  :"  keyword"  ,"  $"  :{"  id"  :"  k0240"  },"  $$"  :[{"  #name"  :"  text"  ,"  _"  :"  vesicular stomatitis virus
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