Background. Inactivated influenza vaccines are manufactured using either split-virion or subunit methods. These 2 methods produce similar hemagglutinin antibody responses, but different cellular immune responses.
Methods. We compared the effectiveness of split-virion influenza vaccines to that of subunit influenza vaccines using prospectively collected data from adults aged ≥50 years who sought care for acute respiratory illness during 3 influenza seasons: 2008–2009, 2010–2011, and 2011–2012 using a case-positive, control test–negative study design.
Results. Complete data were available for 539 participants, of whom 68 (12.6%) had influenza detected. Influenza-infected patients were younger (P < .001), were more likely to have received no vaccine or the subunit influenza vaccine than the split-virion vaccine (P < .001), and more likely to have sought care in either the emergency department or the acute care clinic than the hospital (P = .001). Split-virion vaccine effectiveness was 77.8% (95% confidence interval [CI], 58.5%–90.3%) compared with subunit vaccine effectiveness of 44.2% (95% CI, −11.8% to 70.9%), giving a difference in vaccine effectiveness of 33.5% (95% CI, 6.9%–86.7%).
Conclusions. Studies need to be done to further explore if there are differences in clinical effectiveness in older adults for the 2 vaccine manufacturing methods.