Influenza B Circulation and Vaccine Effectiveness Against Medically Attended Outpatient Influenza B Illness, United States, 2016–17 Through 2024–25

Background Influenza B vaccine effectiveness (VE) has varied by season, lineage, antigenic drift, and vaccine composition. After B/Yamagata detection ceased globally, trivalent vaccines containing B/Victoria were reintroduced in 2024–25. We evaluated influenza B circulation and VE across eight analyzed seasons spanning this transition. Methods Ambulatory patients aged ≥6 months with acute respiratory illness were enrolled at U.S. Flu VE Network sites during eight influenza seasons from 2016–17 through 2024–25; 2020–21 was excluded because influenza circulation was negligible. Participants were tested by RT-PCR. Lineage-specific VE was estimated using a test-negative design and logistic regression adjusted for age, sex, race/ethnicity, calendar time, and study site. VE was reported for season-lineage strata with ≥50 influenza B cases. Results Among 65,773 participants, 3,629 influenza B cases were included in lineage-specific VE analyses (1,507 B/Yamagata; 2,122 B/Victoria). Six of 10 season-lineage strata met the reporting threshold. B/Victoria VE was 58% (95% CI, 28%–77%) in 2016–17, 51% (43%–57%) in 2019–20, 78% (71%–84%) in 2023–24, and 39% (14%–56%) in 2024–25. B/Yamagata VE was 55% (46%–63%) in 2016–17 and 49% (40%–56%) in 2017–18. Conclusions Influenza vaccines protected against medically attended outpatient influenza B illness, although VE varied by season. Continued VE monitoring and genetic surveillance are needed to detect emerging influenza B viruses and inform vaccine strain selection.