Immunogenicity and reactogenicity of high- vs. standard-dose trivalent inactivated influenza vaccine in healthcare workers: a pilot randomized controlled trial.

Abstract

OBJECTIVES\nTo compare immunogenicity, reactogenicity and acceptability of high- and standard-dose trivalent inactivated influenza vaccine (HDTIV, SDTIV) in 18- to 64-year-olds.\n\n\nMETHODS\nWe randomized 18- to 64-year-olds to HDTIV or SDTIV in two consecutive years. We collected serum on days 0 and 21, measured haemagglutination inhibition geometric mean titres (GMT) and compared seroconversion, day 21 titres, seroprotection, reactogenicity and acceptability.\n\n\nRESULTS\nImmunogenicity was evaluable in 42 of 47 2014 participants, all 33 both-year participants and 87 of 90 2015-only participants. First-dose HDTIV recipients experienced seroconversion more frequently than SDTIV recipients to A(H3N2) in 2014 (13/21, 62% vs. 4/21, 19%, p 0.01) and to all vaccine strains in 2015: (A(H1N1): 24/42, 57% vs. 15/59, 25%; A(H3N2): 42/42, 100% vs. 47/59, 80%; B: 25/42, 60% vs. 13/59, 22%; all p <0.01). Day 21 haemagglutination inhibition GMT were higher in first and two sequential-year HDTIV vs. SDTIV recipients: A(H1N1): GMT 749 and 768 vs. 384 (p <0.0001, p 0.002); A(H3N2): 1238 and 956 vs. 633 (p 0.0003, p 0.1); and B: 1113 and 1086 vs. 556 (p 0.0005, p 0.02). HDTIV was more reactogenic (local pain score 3 vs. 1 of 10 on day 0/1, p 0.0003), but recipients were equally willing to be revaccinated (HDTIV: 76/83 (92%); SDTIV: 76/80 (95%), p 0.54). The ratios of day 21 GMT in SDTIV recipients vaccinated in 0 to 4 prior years to those in SDTIV and HDTIV recipients vaccinated in 15 or more prior years were A(H1N1): 3.73 and 1.38; A(H3N2) 3.07 and 1.16; and B: 2.01 and 1.21.\n\n\nCONCLUSIONS\nHDTIV is more immunogenic and reactogenic and as acceptable as SDTIV in 18- to 64-year-olds.