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. We performed a nationwide test-negative case-control study within the US Veterans Affairs Healthcare System 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. These data underscore the importance of strain match to maximize the public health impact of COVID-19 vaccination. ### Competing Interest Statement Haley J. Appaneal has received research funding from Pfizer. Aisling R. Caffrey has received research funding from AbbVie, Merck, and Pfizer. Kerry L. LaPlante has received research funding from AbbVie, Merck, and Pfizer and has been an advisor for Ferring Pharmaceuticals, AbbVie, and Seres Therapeutics. Laura Puzniak, Evan J. Zasowski, Luis Jodar, and John M. McLaughlin are employees and shareholders of Pfizer Inc. ### Funding Statement Pfizer provided funding to the VA Providence Healthcare System for data analysis and manuscript development. HJA, ARC, VVL and KLL are employees of the VA Providence Healthcare System. ### Author Declarations I confirm all relevant ethical guidelines have been followed, and any necessary IRB and/or ethics committee approvals have been obtained. Yes The details of the IRB/oversight body that provided approval or exemption for the research described are given below: This study was determined to be exempt by the VA Providence Healthcare System (VAPHS) Institutional Review Board (IRB) and approved by the VAPHS Research and Development Committee. As this was a retrospective study of existing health records and exempt from IRB review, informed consent requirements are not applicable. I confirm that all necessary patient/participant consent has been obtained and the appropriate institutional forms have been archived, and that any patient/participant/sample identifiers included were not known to anyone (e.g., hospital staff, patients or participants themselves) outside the research group so cannot be used to identify individuals. Yes I understand that all clinical trials and any other prospective interventional studies must be registered with an ICMJE-approved registry, such as ClinicalTrials.gov. I confirm that any such study reported in the manuscript has been registered and the trial registration ID is provided (note: if posting a prospective study registered retrospectively, please provide a statement in the trial ID field explaining why the study was not registered in advance). Yes I have followed all appropriate research reporting guidelines, such as any relevant EQUATOR Network research reporting checklist(s) and other pertinent material, if applicable. Yes The study data may be made available upon reasonable request and approval by the Department of Veterans Affairs.