JVAC
21164
S0264-410X(19)31066-7
10.1016/j.vaccine.2019.08.016
The Author(s)
Safety and immunogenicity of high-dose quadrivalent influenza vaccine in adults ≥65 years of age: A phase 3 randomized clinical trial
Lee-Jah
Chang
a
⁎
Lee-Jah.Chang@sanofi.com
Ya
Meng
a
Helene
Janosczyk
a
Victoria
Landolfi
a
H. Keipp
Talbot
b
for the QHD00013 Study Group
a
Sanofi Pasteur, 1 Discovery Dr, Swiftwater, PA 18370, USA
Sanofi Pasteur
1 Discovery Dr
Swiftwater
PA
18370
USA
Sanofi Pasteur, 1 Discovery Dr, Swiftwater, PA 18370, USA
b
Vanderbilt University Medical Center, 1161 21st Avenue South, Nashville, TN 37232, USA
Vanderbilt University Medical Center
1161 21st Avenue South
Nashville
TN
37232
USA
Vanderbilt University Medical Center, 1161 21st Avenue South, Nashville, TN 37232, USA
⁎
Corresponding author.
Highlights
•
High-dose trivalent influenza vaccine is licensed for adults ≥65 years of age.
•
A quadrivalent formulation with antigen from both B lineages has been developed.
•
Adding the second B strain improved immunogenicity against the added strain.
•
Immunogenicity against the other strains remained the same.
•
The vaccine’s tolerability was unaffected by adding the second B strain.
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
High-dose influenza vaccine
Quadrivalent influenza vaccine
Elderly adults
Immunogenicity
Safety
Clinical trial
KBJ00000000012181
2020-01-30T01:49:12
S300.1
S300
S0264-410X(19)31066-7
10.1016/j.vaccine.2019.08.016
JVAC
0264-410X
21164
FLA
NON-CRC
UNLIMITED
NONE
2019-08-17T20:05:45Z
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