Antibody Responses to Influenza A/H1N1pdm09 Virus After Pandemic and Seasonal Influenza Vaccination in Healthcare Workers: A 5-Year Follow-up Study

Abstract

Abstract Background The 2009 influenza pandemic was caused by the A/H1N1pdm09 virus, which was subsequently included in the seasonal vaccine, up to 2016/2017, as the A/H1N1 strain. This provided a unique opportunity to investigate the antibody response to H1N1pdm09 over time. Methods Healthcare workers (HCWs) were immunized with the AS03-adjuvanted H1N1pdm09 vaccine in 2009 (N = 250), and subsequently vaccinated with seasonal vaccines containing H1N1pdm09 for 4 seasons (repeated group), <4 seasons (occasional group), or no seasons (single group). Blood samples were collected pre and at 21 days and 3, 6, and 12 months after each vaccination, or annually (pre-season) from 2010 in the single group. The H1N1pdm09-specific antibodies were measured by the hemagglutination inhibition (HI) assay. Results Pandemic vaccination robustly induced HI antibodies that persisted above the 50% protective threshold (HI titers ≥ 40) over 12 months post-vaccination. Previous seasonal vaccination and the duration of adverse events after the pandemic vaccination influenced the decision to vaccinate in subsequent seasons. During 2010/2011–2013/2014, antibodies were boosted after each seasonal vaccination, although no significant difference was observed between the repeated and occasional groups. In the single group without seasonal vaccination, 32% of HCWs seroconverted (≥4-fold increase in HI titers) during the 4 subsequent years, most of whom had HI titers <40 prior to seroconversion. When excluding these seroconverted HCWs, HI titers gradually declined from 12 to 60 months post–pandemic vaccination. Conclusions Pandemic vaccination elicited durable antibodies, supporting the incorporation of adjuvant. Our findings support the current recommendation of annual influenza vaccination in HCWs. Clinical Trials Registration NCT01003288.