Activity of convalescent and vaccine serum against SARS-CoV-2 Omicron

Nature. 2022 Feb;602(7898):682-688. doi: 10.1038/s41586-022-04399-5. Epub 2021 Dec 31.


The Omicron (B.1.1.529) variant of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) was initially identified in November 2021 in South Africa and Botswana, as well as in a sample from a traveller from South Africa in Hong Kong1,2. Since then, Omicron has been detected globally. This variant appears to be at least as infectious as Delta (B.1.617.2), has already caused superspreader events3, and has outcompeted Delta within weeks in several countries and metropolitan areas. Omicron hosts an unprecedented number of mutations in its spike gene and early reports have provided evidence for extensive immune escape and reduced vaccine effectiveness2,4-6. Here we investigated the virus-neutralizing and spike protein-binding activity of sera from convalescent, double mRNA-vaccinated, mRNA-boosted, convalescent double-vaccinated and convalescent boosted individuals against wild-type, Beta (B.1.351) and Omicron SARS-CoV-2 isolates and spike proteins. Neutralizing activity of sera from convalescent and double-vaccinated participants was undetectable or very low against Omicron compared with the wild-type virus, whereas neutralizing activity of sera from individuals who had been exposed to spike three or four times through infection and vaccination was maintained, although at significantly reduced levels. Binding to the receptor-binding and N-terminal domains of the Omicron spike protein was reduced compared with binding to the wild type in convalescent unvaccinated individuals, but was mostly retained in vaccinated individuals.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • 2019-nCoV Vaccine mRNA-1273 / immunology
  • Adult
  • Antibodies, Monoclonal / immunology
  • Antibodies, Neutralizing / immunology*
  • Antibodies, Viral / immunology
  • BNT162 Vaccine / administration & dosage
  • BNT162 Vaccine / immunology
  • COVID-19 / immunology*
  • COVID-19 / transmission
  • COVID-19 / virology*
  • COVID-19 Vaccines / immunology*
  • Convalescence*
  • Female
  • Humans
  • Immune Evasion / immunology*
  • Immune Sera / immunology*
  • Immunization, Secondary
  • Models, Molecular
  • Neutralization Tests
  • SARS-CoV-2 / classification
  • SARS-CoV-2 / genetics
  • SARS-CoV-2 / immunology*
  • Spike Glycoprotein, Coronavirus / chemistry
  • Spike Glycoprotein, Coronavirus / genetics
  • Spike Glycoprotein, Coronavirus / immunology


  • Antibodies, Monoclonal
  • Antibodies, Neutralizing
  • Antibodies, Viral
  • COVID-19 Vaccines
  • Immune Sera
  • Spike Glycoprotein, Coronavirus
  • spike protein, SARS-CoV-2
  • 2019-nCoV Vaccine mRNA-1273
  • BNT162 Vaccine

Supplementary concepts

  • SARS-CoV-2 variants