Effectiveness of BNT162b2 XBB vaccine in the US Veterans Affairs Healthcare System

Data evaluating effectiveness of XBB.1.5-adapted vaccines against JN.1-related endpoints are scarce. This nationwide test-negative case-control study within the US Veterans Affairs Healthcare System aims to estimate vaccine effectiveness (VE) of BNT162b2 XBB.1.5-adapted vaccine compared to not receiving an XBB vaccine of any kind against COVID-19 hospitalization, emergency department or urgent care visits (ED/UC), and outpatient visits. Between September 25, 2023 and January 31, 2024, effectiveness was 24-35% during a period of JN.1 predominance and 50-61% during XBB predominance across all outcomes. VE within 60 days of vaccination during the likely JN.1 period was 32% (95% confidence interval 3-52%) against hospitalization, 41% (23-54%) against ED/UC visits, and 31% (1-52%) against outpatient visits. Corresponding VE during the likely XBB period was 62% (44-74%), 52% (37-63%), and 50% (25-66%) by setting, respectively. Here, we show the importance of strain match to maximize the public health impact of COVID-19 vaccination.