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Clinical Trial
. 2021 Dec 2;17(12):5475-5486.
doi: 10.1080/21645515.2021.1983387. Epub 2021 Oct 29.

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

Stephanie Pepin  1 , Jean-François Nicolas  2 , Henryk Szymanski  3 , Isabel Leroux-Roels  4 , Thomas Schaum  5 , Marc Bonten  6 , Giancarlo Icardi  7 , Anju Shrestha  8 , Cynthia Tabar  1 ; QHD00011 study team
Affiliations
Clinical Trial

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

Stephanie Pepin et al. Hum Vaccin Immunother. .

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.

Keywords: High-dose influenza vaccine; Phase III trial; immunogenicity; influenza vaccination; older adults; safety.

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Conflict of interest statement

All authors acquired, analyzed, or interpreted data; drafted or critically revised the manuscript; approved the submitted version; and agreed to be accountable for its accuracy and integrity. In addition, SP and CT designed the study.

SP, AS, and CT are Sanofi Pasteur employees and may/may not hold stock/shares in the company.

MB reports fees paid to UMC Utrecht from Sanofi Pasteur, during the conduct of the study; fees paid to UMC Utrecht from Sanofi Pasteur, Janssen, and Pfizer, outside the submitted work. HS reports personal fees, nonfinancial support and other from Sanofi Pasteur during the conduct of the study; personal fees, nonfinancial support and other from Ablynx, GSK, Janssen, and Pfizer, outside the submitted work; also, personal fees and other from MSD and Seqirus, outside the submitted work.

IL-R reports fees paid to Ghent University Hospital from Sanofi Pasteur during the conduct of the study; fees paid to Ghent University Hospital from GSK, MSD, J&J and Curevac outside the submitted work. J-FN, TS, and GI have nothing to disclose.

Figures

Figure 1.
Figure 1.
Participant disposition.
Figure 2.
Figure 2.
Immunogenicity primary objective: Superiority of IIV4-HD compared with IIV4-SD using GMTs at D 28 after vaccination – Full Analysis Set. (a) Geometric mean titer ratios for each strain in each analysis group. GMTRs calculated as geometric mean of individual ratios at D 28 and 0. Labels GMTR (95% CI). (b) GMTRs for each strain in each analysis group. GMT, geometric mean titer; GMTR, geometric mean titer ratio; IIV4-HD, quadrivalent high-dose inactivated influenza vaccine; IIV4-SD, standard-dose quadrivalent influenza vaccine.
Figure 3.
Figure 3.
Summary of neutralizing Ab titers (SN assay) at baseline and at D 28 after vaccination – Full Analysis Set SN Subset. Ab, antibody; IIV4-HD, quadrivalent high-dose inactivated influenza vaccine; IIV4-SD, standard-dose quadrivalent influenza vaccine; SN, seroneutralization.
Figure 4.
Figure 4.
Summary of anti-NA antibody response (ELLA) at baseline and at D 28 after vaccination – Full Analysis Set-NA Subset. Geometric mean titer ratios calculated from GMT at D 28/GMT at D 0. IIV4-HD, quadrivalent high-dose inactivated influenza vaccine; IIV4-SD, standard-dose quadrivalent influenza vaccine; NA, neuraminidase.
Figure 5.
Figure 5.
Solicited injection-site reactions after vaccine injection, by maximum intensity during the solicited period (7 d following vaccination) – Safety Analysis Set. (a) 60–64 y IIV4-HD. (b) 60–64 y IIV4-SD. (c) ≥65 y IIV4-HD. (d) ≥65 y IIV4-SD. IIV4-HD, quadrivalent high-dose inactivated influenza vaccine; IIV4-SD, standard-dose quadrivalent influenza vaccine.
Figure 6.
Figure 6.
Solicited systemic reactions after vaccine injection, by maximum intensity during the solicited period (7 d after vaccination) – Safety Analysis Set. (a) 60–64 y IIV4-HD. (b) 60–64 y IIV4-SD. (c) ≥65 y IIV4-HD. (d) ≥65 y IIV4-SD. IIV4-HD, quadrivalent high-dose inactivated influenza vaccine; IIV4-SD, standard-dose quadrivalent influenza vaccine.
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