Correlates of protection against SARS-CoV-2 Omicron variant and anti-spike antibody responses after a third/booster vaccination or breakthrough infection in the UK general population

This research has not been peer-reviewed. It is a preliminary report that should not be regarded as conclusive, guide clinical practice or health-related behaviour, or be reported in news media as established information.

Following primary SARS-CoV-2 vaccination, understanding the relative extent of protection against SARS-CoV-2 infection from boosters or from breakthrough infections (i.e. infection in the context of previous vaccination) has important implications for vaccine policy. In this study, we investigated correlates of protection against Omicron BA.4/5 infections and anti-spike IgG antibody trajectories after a third/booster vaccination or breakthrough infection following second vaccination in 154,149 adults ≥18y from the United Kingdom general population. We found that higher anti-spike IgG antibody levels were associated with increased protection against Omicron BA.4/5 infection and that breakthrough infections were associated with higher levels of protection at any given antibody level than booster vaccinations. Breakthrough infections generated similar antibody levels to third/booster vaccinations, and the subsequent declines in antibody levels were similar to or slightly slower than those after third/booster vaccinations. Taken together our findings show that breakthrough infection provides longer lasting protection against further infections than booster vaccinations. For example, considering antibody levels associated with 67% protection against infection, a third/booster vaccination did not provide long-lasting protection, while a Delta/Omicron BA.1 breakthrough infection could provide 5-10 months of protection against Omicron BA.4/5 reinfection. 50-60% of the vaccinated UK population with a breakthrough infection would still be protected by the end of 2022, compared to <15% of the triple-vaccinated UK population without previous infection. Although there are societal impacts and risks to some individuals associated with ongoing transmission, breakthrough infection could be an efficient immune-boosting mechanism for subgroups of the population, including younger healthy adults, who have low risks of adverse consequences from infection.

Author list

 

Affiliations:

  1. Nuffield Department of Medicine, University of Oxford, Oxford, UK
  2. Big Data Institute, Nuffield Department of Population Health, University of Oxford, Oxford, UK
  3. The Francis Crick Institute, 1 Midland Road, London, UK
  4. Division of infection and immunity, University College London, London, UK
  5. Department of Infectious Diseases and Microbiology, Oxford University Hospitals NHS Foundation Trust, John Radcliffe Hospital, Oxford, UK
  6. The National Institute for Health Research Health Protection Research Unit in Healthcare Associated Infections and Antimicrobial Resistance at the University of Oxford, Oxford, UK
  7. The National Institute for Health Research Oxford Biomedical Research Centre, University of Oxford, Oxford, UK
  8. European Centre for Environment and Human Health, University of Exeter, Truro, UK
  9. Office for National Statistics, Newport, UK
  10. Office of the Regius Professor of Medicine, University of Oxford, Oxford, UK
  11. Wellcome Trust, London, UK
  12. Nuffield Department of Orthopaedics, Rheumatology and Musculoskeletal Sciences, University of Oxford, Oxford, UK
  13. MRC Clinical Trials Unit at UCL, UCL, London, UK
  14. Health Economics Research Centre, Nuffield Department of Population Health, University of Oxford, Oxford, UK

Authors:

Jia Wei, Philippa C. Matthews, Nicole Stoesser, John N Newton, Ian Diamond, Ruth Studley, Nick Taylor, John I Bell, Jeremy Farrar, Jaison Kolenchery, Brian D. Marsden, Sarah Hoosdally, E Yvonne Jones, David I Stuart, Derrick W. Crook, Tim E. A. Peto, A. Sarah Walker, Koen B. Pouwels, David W. Eyre, the COVID-19 Infection Survey team

Novel Coronavirus SARS-CoV-2

10.1101/2022.11.29.22282916

MedRxiv

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