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Dynamics of SARS-CoV-2 VOC Neutralization and Novel mAb Reveal Protection against Omicron.

Linhui HaoTien-Ying HsiangRonit R DalmatRenee C IretonJennifer F MortonCaleb StokesJason NetlandMalika HaleChris ThouvenelAnna WaldNicholas M FrankoKristen HudenHelen Y ChuAlex SigalAlexander L GreningerSasha W TilesLynn K BarrettWesley C Van VoorhisJennifer MuntTrevor ScobeyRalph S BaricDavid J RawlingsMarion PepperPaul K DrainMichael Gale
Published in: Viruses (2023)
New variants of SARS-CoV-2 continue to emerge and evade immunity. We isolated SARS-CoV-2 temporally across the pandemic starting with the first emergence of the virus in the western hemisphere and evaluated the immune escape among variants. A clinic-to-lab viral isolation and characterization pipeline was established to rapidly isolate, sequence, and characterize SARS-CoV-2 variants. A virus neutralization assay was applied to quantitate humoral immunity from infection and/or vaccination. A panel of novel monoclonal antibodies was evaluated for antiviral efficacy. We directly compared all variants, showing that convalescence greater than 5 months post-symptom onset from ancestral virus provides little protection against SARS-CoV-2 variants. Vaccination enhances immunity against viral variants, except for Omicron BA.1, while a three-dose vaccine regimen provides over 50-fold enhanced protection against Omicron BA.1 compared to a two-dose. A novel Mab neutralizes Omicron BA.1 and BA.2 variants better than the clinically approved Mabs, although neither can neutralize Omicron BA.4 or BA.5. Thus, the need remains for continued vaccination-booster efforts, with innovation for vaccine and Mab improvement for broadly neutralizing activity. The usefulness of specific Mab applications links with the window of clinical opportunity when a cognate viral variant is present in the infected population.
Keyphrases
  • sars cov
  • copy number
  • respiratory syndrome coronavirus
  • primary care
  • genome wide
  • gene expression
  • oxidative stress
  • zika virus
  • amino acid