Six-monthly versus annual influenza vaccination in older adults in the tropics: an observer-blind, active-comparator controlled, randomised superiority trial

Background:
Antibody titres and vaccine effectiveness decline within six months after influenza vaccination in older adults. Biannual vaccination may be necessary to provide year-round protection in the tropics where influenza circulates throughout the year.
Methods:
Tropical Influenza Control Strategies (TROPICS1) was a single-centre, 1:1 randomised, observer-blinded, active-comparator controlled, superiority study in 200 community-resident adults aged ≥65 years. Participants received standard-dose trivalent inactivated influenza vaccination (IIV3) at enrolment, and either tetanus-diphtheria-pertussis vaccination or IIV3 six months later. Primary outcome was the proportion of participants with haemagglutination-inhibition (HI) geometric mean titre (GMT) ≥1:40 one month after the second vaccination (Month 7). Secondary outcomes included GMTs to Month 12, the incidence of influenza-like illness (ILI), and adverse reactions after vaccination.
Results:
At Month 7, the proportion of participants with a HI tire ≥1:40 against A/H1N1 increased by 21.4% (95% CI 8.6-33.4) in the six-monthly vaccination group. This proportion was not significantly higher for A/H3N2 (4.3, 95% CI -1.1-10.8) or B (2.1, 95% CI -2.0-7.3). Six-monthly vaccination significantly increased GMTs against A/H1N1 and A/H3N2 at Month 7, but not B. Participants receiving repeat IIV3 reported a significantly lower incidence of ILI in the six months after the second vaccination (relative vaccine effectiveness 57.1%, 95% CI 0.6-81.5). The frequency of adverse events was similar after first or second influenza vaccination.