Immunogenicity of twice-annual influenza vaccination in older adults in Hong Kong: a randomized controlled trial

Abstract

Learning Objective: Compare the potential advantages and disadvantages of twice‐annual influenza vaccination in locations with year‐round influenza activity to describe the considerations in designing national influenza vaccination program in countries with different seasonal patterns of influenza activity Abstract: Older adults are advised to receive inactivated influenza vaccination (IIV) annually in Hong Kong. However, vaccine protection may not span 12 months [1], and twice‐annual vaccination could improve protection in locations with year‐round activity [2]. We conducted a randomized controlled trial of once‐annual versus twice‐annual influenza vaccination in adults 70–79 years of age in Hong Kong. All participants received northern hemisphere quadrivalent IIV in autumn/winter 2016–2017 (Round 1). In spring/summer 2017 (Round 2) participants were then randomized to receive placebo or the southern hemisphere trivalent IIV containing a new A(H1N1) antigen but unchanged A(H3N2) and influenza B(Victoria) antigens compared to Round 1. In autumn/winter 2017–2018 (Round 3), all participants received northern hemisphere quadrivalent IIV with identical vaccine antigens to Round 2 plus the same B(Yamagata) antigen used in Round 1. Sera were collected prior to and one month after each vaccination for testing by the hemagglutination inhibition (HAI) assay against vaccine strains. We compared mean‐fold rises in HAI titers from pre‐ to post‐vaccination, and geometric mean titers (GMTs) after vaccination. A total of 404 participants were enrolled. Participants who received IIV in Round 2 had significantly higher GMTs against the vaccine strains of influenza A(H1N1) and A(H3N2) between Rounds 2 and 3. In both groups, mean‐fold rises and post‐vaccination GMTs against all vaccine strains were statistically significantly lower in Round 3 than Round 1. Receipt of IIV versus placebo in Round 2 did not have a statistically significant effect on post‐vaccination GMTs in Round 3. Vaccination in spring/summer 2017 provided improved HAI titers that could bridge protection between annual doses in older adults. The trial will continue to explore patterns in antibody titers in subsequent years when vaccine strains change. References: 1. Ferdinands JM, Fry AM, Reynolds S, et al. Intraseason waning of influenza vaccine protection: Evidence from the US Influenza Vaccine Effectiveness Network, 2011‐12 through 2014‐15. Clin. Infect. Dis. 2017;64(5):544‐550. 2. Tam YH, Valkenburg SA, Perera R, et al. Immune responses to twice‐annual influenza vaccination in older adults in Hong Kong. Clin. Infect. Dis. 2018;66(6):904‐912.