Safety and immunogenicity of a quadrivalent influenza vaccine in adults aged 60 years or above: a phase III randomized controlled clinical study

Abstract

To control seasonal influenza epidemics in elders, a quadrivalent, inactivated, split-virion influenza vaccine (IIV4) comprising A and B lineages is produced for young individuals and adults aged ≥60 years. In this phase III, randomized, double-blind, active-controlled trial, we compared safety and immunogenicity of IIV4 with a licensed quadrivalent inactivated vaccine (IIV4-HL) produced by Hualan Biological Engineering during the 2019 influenza season. Participants were randomly assigned to receive IIV4 (n = 959) or IIV4-HL (n = 959). Compared to IIV4-HL, geometric mean titers (GMT) of hemagglutination inhibition (HAI) titers and seroconversion rate (SCR) of IIV4 demonstrated better antibody responses in A lineages (H1N1 and H3N2) (P < .01) and equivalent antibody responses in B lineages (B/Yamagata and B/Victoria) (P > .01) in both age groups. After immunization, IIV4 provided a satisfactory SCR and seroprotection rate (SPR) in elders. No discernible variation in immunogenicity was observed between the two age cohorts. In both age groups, IIV4 and IIV4-HL recipients experienced similar levels of solicited and unsolicited adverse events (AEs), and the incidence of AEs was low in both vaccine groups. Most AEs were of mild-to-moderate severity and no grade 3 AEs in IIV4 group, but AEs in adults aged 60-65 were little higher than in adults over 65 years in IIV4 and IIV4-HL groups (IIV4: 14.66% vs. 10.36%; IIV4-HL:14.67% vs. 11.43%). Totally, IIV4 was generally well tolerated and induced high antibody titers against all four influenza strains in elderly, making it a compelling alternative for the elderly aged ≥60 years.Trial registration: Clinical Trials.gov: 2015L00649-2.

Immunogenicity of a trivalent influenza vaccine and persistence of induced immunity in adults aged ≥60 years in Taizhou City, Zhejiang Province, China, during the 2018–2019 season

“…Because of age-related declines in immune function, older adults exhibit lower antibody responses to influenza vaccination, especially for influenza B strains, compared with younger adults. 19 , 20 A recent review of antibody responses in 31 influenza vaccine studies conducted from 1986 to 2002 concluded that adults aged ≥60 years were 2–4 times less likely to seroconvert or achieve protective HI antibody titers after influenza vaccination, compared with young adults. 21 Traditional inactivated influenza vaccines are often only modestly immunogenic.…”

Safety and immunogenicity of a quadrivalent, inactivated, split-virion influenza vaccine (IIV4-W) in healthy people aged 3-60 years: a phase III randomized clinical noninferiority trial

“…IIV4-W containing both of the B lineage influenza strain antigens could decrease influenza hospitalization and could be considered a candidate influenza vaccine against seasonal influenza in children, adults and elderly individuals. 8 …”

“…Hemagglutination inhibition (HI) assays were performed for the serological antibody assessments using the same procedure as previously reported. 8 Twenty-five microliters of serum was used for HI antibody detection of one subtype strain, and the HI titer was defined as the dilution factor of serum completely inhibiting hemagglutination.…”

“…The phase III trial of IIV4-W by the Wuhan Institute of Biological Products Co. Ltd. was completed to evaluate the tolerability and immunogenicity in elderly individuals aged 60 years above in 2019. 8 To investigate the safety and immunogenicity of IIV4-W in children and older adults as a candidate influenza vaccine, we conducted a phase III noninferiority trial that compared IIV4-W with two controls (TIV1 and TIV2 produced by Changchun Institute of Biological Products Co. Ltd. and approved by the National Institutes for Food and Drug Control that included two influenza A strains, TIV1 containing influenza B/Yamagata and TIV2 containing B/Victoria) as the chosen influenza vaccine in China in participants aged 3–60 years.…”