Strong peak immunogenicity but rapid antibody waning following third vaccine dose in older residents of care homes
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 Wu, Ruth Harvey, Edward J Carr, Crick COVID Immunity Pipeline, Bobbi Clayton, Sina Namjou, Vanessa Silva, Meghan Poulten, Philip Bawumia, Murad Miah, Samuel Sade, Mauro Miranda, Tom Taylor, Ilenia D’Angelo, Mercedes Cabrera Jarana, Mahbubur Rahman, Janet Abreu, Sandeep Sandhar, Neil A. Bailey, Simon Caidan, Marie B. Caulfield, Mary Wu, Ruth Harvey, Lorin Adams, Caitlin Kavanagh, Scott Warchal, Chelsea Sawyer, Mike Gavrielides, Jag Kandasamy, Karen Ambrose, Amy Strange, Titilayo Abiola, Nicola O’Reilly, Philip Hobson, Ana Agau-Doce, Emma Russell, Andrew Riddell, Svend Kjær, Annabel Borg, Chloë Roustan, Christophe J. Queval, Rachel Ulferts, Charles Swanton, Sonia Gandhi, Steve Gamblin, Rupert Beale, Oliver Stirrup, Madhumita Shrotri, Borscha Azmi, Christopher Fuller, Verity Baynton, Aidan Irwin-Singer, Andrew Hayward, Andrew Copas, Laura Shallcross, Paul Moss
Abstract
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.