Separating the effects of immune waning and viral evolution on COVID-19 vaccine effectiveness reveals improved effectiveness of updated vaccines
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The continued evolution of SARS-CoV-2 has led to regular updates of the COVID-19 vaccine immunogen. However, the exact benefits of these updates for vaccine effectiveness in a real world context are difficult to evaluate. We performed a comprehensive meta-analysis of booster vaccine effectiveness in studies identified through the ViewHub systematic review. We integrated evidence from 44 studies reporting on effectiveness of mRNA booster vaccines containing XBB.1.5, JN.1 and KP.2 immunogens to assess the combined impact of booster immunogen, time since vaccination and calendar time at which a study was conducted. We estimate that the relative risk of severe disease increases by 9% [95%CI 7.4-10.5] each month following booster administration, likely due to antibody waning, and by an additional 2.4% [95%CI 1.2-3.6] for each calendar month, likely due to antigenic drift. Our findings show that COVID-19 booster vaccine effectiveness declines both with time after vaccination as well as calendar time since the vaccine immunogen emerged. This reinforces the need for regularly and timely vaccine immunogen updates.
