Predicting long-term waning of anti-spike antibody-dependent protection against COVID-19 across diverse SARS-CoV-2 immune histories
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SARS-CoV-2 mRNA vaccines elicit robust anti-spike (anti-S) and neutralizing antibody responses; however, their kinetics beyond one year and variation across complex combination of vaccination and infection histories remain unclear. We analyzed data from 25,800 Japanese adults from four nationwide sero-epidemiological surveys (December 2021 to March 2023). Using Bayesian hierarchical models, we characterized long-term antibody trajectories stratified by vaccine doses (2–5), infection history (uninfected, pre-Omicron, Omicron), and demographics. In uninfected participants, 3–5 vaccine doses induced higher peak anti-S titers and slower waning than two doses. Notably, a history of Omicron infection, but not a history of an Omicron-adapted bivalent booster vaccination, was associated with sustained high anti-S and Omicron BA.5-neutralizing titers for over two years, irrespective of the number of vaccine doses. We then integrated these antibody-waning models with a correlates-of-protection model to predict the long-term decline in protection against symptomatic infection, stratified by specific immune history. These models provide a flexible framework for optimizing future vaccine-dosing intervals to minimize symptomatic infection risk across populations with diverse immune backgrounds.
