Safety and immunogenicity of high-dose quadrivalent influenza vaccine in adults ≥65 years of age: A phase 3 randomized clinical trial

Lee-Jah Chang; Ya Meng; Helene Janosczyk; Victoria Landolfi; H Keipp Talbot; QHD00013 Study Group

doi:10.1016/j.vaccine.2019.08.016

Safety and immunogenicity of high-dose quadrivalent influenza vaccine in adults ≥65 years of age: A phase 3 randomized clinical trial

Vaccine. 2019 Sep 16;37(39):5825-5834. doi: 10.1016/j.vaccine.2019.08.016. Epub 2019 Aug 17.

Authors

Lee-Jah Chang¹, Ya Meng², Helene Janosczyk², Victoria Landolfi², H Keipp Talbot³; QHD00013 Study Group

Affiliations

¹ Sanofi Pasteur, 1 Discovery Dr, Swiftwater, PA 18370, USA. Electronic address: Lee-Jah.Chang@sanofi.com.
² Sanofi Pasteur, 1 Discovery Dr, Swiftwater, PA 18370, USA.
³ Vanderbilt University Medical Center, 1161 21st Avenue South, Nashville, TN 37232, USA.

PMID: 31431411
DOI: 10.1016/j.vaccine.2019.08.016

Abstract

Background: A high-dose, split-virion inactivated trivalent influenza vaccine (IIV3-HD; Fluzone® High-Dose, Sanofi Pasteur) is available for adults ≥65 years of age. This study examined the safety and immunogenicity of a quadrivalent high-dose split-virion inactivated influenza vaccine (IIV4-HD).

Methods: This was a randomized, modified double-blind, active-controlled, multi-center trial in healthy adults ≥65 years of age. Subjects were randomized in a 4:1:1 ratio to receive a single intramuscular injection of IIV4-HD, the licensed IIV3-HD, or an IIV3-HD containing the alternate B-lineage strain. Hemagglutination inhibition (HAI), seroneutralisation, and anti-neuraminidase antibody titers were measured at baseline and day 28. Solicited reactions were collected for up to 7 days, unsolicited adverse events up to 28 days, and serious adverse events up to 180 days. The primary immunogenicity objective was to demonstrate that IIV4-HD induces HAI geometric mean titers (GMTs) and seroconversion rates that are non-inferior to those induced by IIV3-HD. Secondary objectives were to describe the safety of IIV4-HD and IIV3-HD and to demonstrate that IIV4-HD induces HAI GMTs and seroconversion rates that are superior to those induced by IIV3-HD not containing the same B-lineage strain.

Results: The study included 2670 adults ≥65 years of age. For all four strains, HAI GMTs and seroconversion rates induced by IIV4-HD were non-inferior to those induced by IIV3-HDs containing the same strains. For both B strains, HAI GMTs and seroconversion rates induced by IIV4-HD were superior to those induced by IIV3-HD not containing the same B-lineage strain. Seroneutralisation and anti-neuraminidase antibody responses, measured in a subset of subjects, were similar. No new safety concerns were identified, and the safety profiles of IIV4-HD and IIV3-HD were similar.

Conclusions: Adding a second B strain in IIV4-HD resulted in improved immunogenicity against the added strain without compromising the immunogenicity of the other strains or the vaccine's tolerability.

Clinical trial registration: NCT03282240.

Keywords: Clinical trial; Elderly adults; High-dose influenza vaccine; Immunogenicity; Quadrivalent influenza vaccine; Safety.

Publication types

Clinical Trial, Phase III
Randomized Controlled Trial
Research Support, Non-U.S. Gov't

MeSH terms

Aged
Antibodies, Viral / immunology
Double-Blind Method
Drug-Related Side Effects and Adverse Reactions / immunology
Female
Hemagglutination Inhibition Tests / methods
Humans
Immunogenicity, Vaccine / immunology*
Influenza B virus / immunology
Influenza Vaccines / adverse effects*
Influenza Vaccines / immunology*
Influenza, Human / immunology*
Influenza, Human / prevention & control*
Injections, Intramuscular / methods
Male
Neuraminidase / immunology
Vaccines, Inactivated / adverse effects
Vaccines, Inactivated / immunology
Virion / immunology

Substances

Antibodies, Viral
Influenza Vaccines
Vaccines, Inactivated
Neuraminidase

Associated data

ClinicalTrials.gov/NCT03282240