Strong peak immunogenicity but rapid antibody waning following third vaccine dose in older residents of care homes

Third-dose coronavirus disease 2019 vaccines are being deployed widely but their efficacy has not been assessed adequately in vulnerable older people who exhibit suboptimal responses after primary vaccination series. This observational study, which was carried out by the VIVALDI study based in England, looked at spike-specific immune responses in 341 staff and residents in long-term care facilities who received an mRNA vaccine following dual primary series vaccination with BNT162b2 or ChAdOx1. Third-dose vaccination strongly increased antibody responses with preferential relative enhancement in older people and was required to elicit neutralization of Omicron. Cellular immune responses were also enhanced with strong cross-reactive recognition of Omicron. However, antibody titers fell 21–78% within 100 d after vaccine and 27% of participants developed a breakthrough Omicron infection. These findings reveal strong immunogenicity of a third vaccine in one of the most vulnerable population groups and endorse an approach for widespread delivery across this population. Ongoing assessment will be required to determine the stability of immune protection.

Author list



  1. Institute of Immunology and Immunotherapy, University of Birmingham, Birmingham, UK
  2. UCL Institute of Health Informatics, London, UK
  3. Covid Surveillance Unit, The Francis Crick Institute, London, UK
  4. Worldwide Influenza Centre, The Francis Crick Institute London, London, UK
  5. The Francis Crick Institute, London, UK
  6. Genotype-to-Phenotype UK National Virology Consortium (G2P-UK), London, UK
  7. UCL Department of Renal Medicine, Royal Free Hospital, London, UK
  8. Health Security Agency, London, UK
  9. Health Data Research UK, London, UK
  10. UCL Institute for Global Health, London, UK


Gokhan Tut, Tara Lancaster, Maria Krutikov, Panagiota Sylla, David Bone, Eliska Spalkova, Christopher Bentley, Umayr Amin, Azar Jadir, Samuel Hulme, Nayandeep Kaur, Elif Tut, Rachel Bruton, Mary Y. Wu, Ruth Harvey, Edward J. Carr, Crick COVID Immunity Pipeline, Rupert Beale, Oliver Stirrup, Madhumita Shrotri, Borscha Azmi, Christopher Fuller, Verity Baynton, Aidan Irwin-Singer, Andrew Hayward, Andrew Copas, Laura Shallcross & Paul Moss 

Novel Coronavirus SARS-CoV-2


Nature Aging