Immune boosting by B.1.1.529 (Omicron) depends on previous SARS-CoV-2 exposure

The Omicron, or Pango lineage B.1.1.529, variant of SARS-CoV-2 carries multiple spike mutations with high transmissibility and partial neutralizing antibody (nAb) escape. Vaccinated individuals show protection from severe disease, often attributed to primed cellular immunity. We investigated T and B cell immunity against B.1.1.529 in triple mRNA vaccinated healthcare workers (HCW) with different SARS-CoV-2 infection histories. B and T cell immunity against previous variants of concern was enhanced in triple vaccinated individuals, but magnitude of T and B cell responses against B.1.1.529 spike protein was reduced. Immune imprinting by infection with the earlier B.1.1.7 (Alpha) variant resulted in less durable binding antibody against B.1.1.529. Previously infection-naïve HCW who became infected during the B.1.1.529 wave showed enhanced immunity against earlier variants, but reduced nAb potency and T cell responses against B.1.1.529 itself. Previous Wuhan Hu-1 infection abrogated T cell recognition and any enhanced cross-reactive neutralizing immunity on infection with B.1.1.529.

Author list



  1. Department of Infectious Disease, Imperial College London, London, UK.
  2. Blizard Institute, Barts and the London School of Medicine and Dentistry, Queen Mary University of London, London, UK.
  3. UK Health Security Agency, Porton Down, UK.
  4. St Bartholomew’s Hospital, Barts Health NHS Trust, London, UK.
  5. Institute of Cardiovascular Science, University College London, London, UK.
  6. Department of Immunology and Inflammation, Imperial College London, London, UK.
  7. Lung Division, Royal Brompton and Harefield Hospitals, Guy’s and St Thomas’ NHS Foundation Trust, London, UK.


Catherine J. Reynolds1†, Corinna Pade2†, Joseph M. Gibbons2†, Ashley D. Otter3†, Kai-Min Lin1, Diana Muñoz Sandoval1, Franziska P. Pieper1, David K. Butler1, Siyi Liu1, George Joy4, Nasim Forooghi4, Thomas A. Treibel4,5, Charlotte Manisty4,5, James C. Moon4,5, COVIDsortium Investigators‡, COVIDsortium Immune Correlates Network‡, Amanda Semper3, Tim Brooks3, Áine McKnight2§, Daniel M. Altmann6§, Rosemary J. Boyton1,7§*

Novel Coronavirus SARS-CoV-2