Protection against SARS-CoV-2 Omicron BA.4/5 variant following booster vaccination or breakthrough infection in the UK
Jia Wei, Philippa C. Matthews, Nicole Stoesser, John Newton, Ian Diamond, Ruth Studley, Nick P. Taylor, John I. Bell, Jeremy Farrar, Jaison Kolenchery, Brian D. Marsden, Sarah Hoosdally, E. Yvonne Jones, David I. Stuart, Derrick W. Crook, Tim Peto, A. Sarah Walker, Koen B. Pouwels, David W. Eyre, the COVID-19 Infection Survey team, Tina Thomas, Daniel Ayoubkhani, Russell Black, Antonio Felton, Megan Crees, Joel W. Jones, Lina Lloyd, Esther Sutherland, Emma Pritchard, Karina-Doris Vihta, George Doherty, James Kavanagh, Kevin Chau, Stephanie B. Hatch, Daniel Ebner, Lucas Martins Ferreira, Thomas Christott, Wanwisa Dejnirattisai, Juthathip Mongkolsapaya, Sarah Cameron, Phoebe Tamblin-Hopper, Magda Wolna, Rachael Brown, Richard J. Cornall, Gavin Screaton, Katrina Lythgoe, David Bonsall, Tanya Golubchik, Helen Fryer, Stuart Cox, Kevin Paddon, Tim James, Thomas House, Julie V. Robotham, Paul Birrell, Helena Jordan, Tim Sheppard, Graham Athey, Dan Moody, Leigh Curry, Pamela Brereton, Ian Jarvis, Anna Godsmark, George Morris, Bobby Mallick, Phil Eeles, Jodie Hay, Harper VanSteenhouse, Jessica Lee, Sean White, Tim Evans, Lisa Bloemberg, Katie Allison, Anouska Pandya, Sophie Davis, David I. Conway, Margaret MacLeod, Chris Cunningham
Abstract
Following primary SARS-CoV-2 vaccination, whether boosters or breakthrough infections provide greater protection against SARS-CoV-2 infection is incompletely understood. Here we investigated SARS-CoV-2 antibody correlates of protection against new Omicron BA.4/5 (re-)infections and anti-spike IgG antibody trajectories after a third/booster vaccination or breakthrough infection following second vaccination in 154,149 adults ≥18 y from the United Kingdom general population. Higher antibody levels were associated with increased protection against Omicron BA.4/5 infection and breakthrough infections were associated with higher levels of protection at any given antibody level than boosters. Breakthrough infections generated similar antibody levels to boosters, and the subsequent antibody declines were slightly slower than after boosters. Together our findings show breakthrough infection provides longer-lasting protection against further infections than booster vaccinations. Our findings, considered alongside the risks of severe infection and long-term consequences of infection, have important implications for vaccine policy.