Immunogenicity and safety of a quadrivalent high-dose inactivated influenza vaccine compared with a standard-dose quadrivalent influenza vaccine in healthy people aged 60 years or older: a randomized Phase III trial

Abstract

A quadrivalent high-dose inactivated influenza vaccine (IIV4-HD) is licensed for adults ≥65 y of age based on immunogenicity and efficacy studies. However, IIV4-HD has not been evaluated in adults aged 60–64 y. This study compared immunogenicity and safety of IIV4-HD with a standard-dose quadrivalent influenza vaccine (IIV4-SD) in adults aged ≥60 y. This Phase III, randomized, modified double-blind, active-controlled study enrolled 1,528 participants aged ≥60 y, randomized 1:1 to a single injection of IIV4-HD or IIV4-SD. Hemagglutination inhibition (HAI) geometric mean titers (GMTs) were measured at baseline and D 28 and seroconversion assessed. Safety was described for 180 d after vaccination. The primary immunogenicity objective was superiority of IIV4-HD versus IIV4-SD, for all four influenza strains 28 d post vaccination in participants aged 60–64 and ≥65 y. IIV4-HD induced a superior immune response versus IIV4-SD in terms of GMTs in participants aged 60–64 y and those aged ≥65 y for all four influenza strains. IIV4-HD induced higher GMTs in those aged 60–64 y than those aged ≥65 y. Seroconversion rates were higher for IIV4-HD versus IIV4-SD in each age-group for all influenza strains. Both vaccines were well tolerated in participants ≥60 y of age, with no safety concerns identified. More solicited reactions were reported with IIV4-HD than with IIV4-SD. IIV4-HD provided superior immunogenicity versus IIV4-SD and was well tolerated in adults aged ≥60 y. IIV4-HD is assumed to offer improved protection against influenza compared with IIV4-SD in adults aged ≥60 y, as was previously assessed for adults aged ≥65 y.

Reply letter to “Immunogenicity and safety of a quadrivalent high-dose inactivated influenza vaccine compared with a standard-dose quadrivalent influenza vaccine in healthy people aged 60 years or older: a randomized Phase III trial”

“…Hence, when communicating about vaccine efficacy, especially for public health decisions, having a complete picture of the data is important, and looking at just one summary measure is not good practice. In line with the extrapolation of superior vaccine efficacy of IIV4HD vaccine vs IIV4SD based on trivalent data as anticipated by Pepin et al 1 similarly, limited differences in NNV numbers may be expected considering IIV4SD vs IIV4HD.…”

“…We read with interest the article from Pepin et al 1 demonstrating that quadrivalent high-dose inactivated influenza vaccine (IIV4HD) generated superior immunogenicity to a standard-dose quadrivalent vaccine (IIV4SD) and was well tolerated with no major safety concerns in adults ≥60 years of age. However, we had a few comments on some of the extrapolated conclusions put forward in the publication.…”

“…The Pepin et al 1 study focused on immunogenicity, which may be considered an indicative biomarker of vaccine efficacy, 3 but the author extrapolated the clinical and health economic benefits highlighted in the real-world setting for the IIV3-HD to the newer IIV4HD vaccine.…”

Saisonale Influenza – Aktuelles zu Epidemiologie, Prävention und Therapie

“…Nach Impfung mit trivalenten Hochdosis-Impfstoffen, die neben den Influenza-Typ-A-Stämmen nur einen der B-Stämme enthalten, kam es in einer randomisierten Doppelblindstudie im Vergleich zu standarddosierten trivalenten Vakzinen zu absolut 0,5 % und relativ 24 % weniger symptomatischen laborbestätigten Influenza-Erkrankungen (1,4 % vs. 1,9 %; 95 % CI 9,7–36,5) 16 . Der von der STIKO empfohlene tetravalente Hochdosis-Impfstoff induzierte bei ≥ 60-jährigen Immunantworten, die denjenigen eines standarddosierten tetravalenten Impfstoffs für alle 4 zirkulierenden Influenzastämme überlegen waren 17 . Nach Modellrechnungen der STIKO könnten durch die hohe Morbidität durch Influenza selbst eine mit 15 % eher restriktiv kalkulierte, verbesserte Impfeffektivität von Hochdosis-Impfstoffen zu einer beträchtlichen Reduktion der Krankheitslast führen.…”

Reply to letter to editor by Hadigal et al. regarding the immunogenicity and safety trial of high-dose influenza vaccine in adults aged ≥60 years

“… 1 We recently published an immunobridging trial demonstrating superior immunogenicity and similar reactogenicity of high dose quadrivalent influenza vaccine (IIV4-HD) vs. standard dose quadrivalent vaccine (IIV4-SD) in adults aged ≥60 years. 2 Hadigal et al from Viatris Inc. commented on IIV4-HD following our publication, 3 and here we would like to address their viewpoints.…”