Journal Article

A randomised phase 2 immunogenicity and safety study of a MF59-adjuvanted quadrivalent subunit inactivated cell-derived influenza vaccine (aQIVc) in adults aged 50 years and older

Essink, Brandon J., Andrade, Coralie, Vermeulen, Wim, Albano, Frank R., de Rooij, Richard, Casula, Daniela, Isakov, Leah

2025

Overview

Influenza poses a significant global healthcare burden, with up to 1 billion infections annually, and poorer outcomes in vulnerable populations such as older adults. Vaccination effectiveness is often lower in elderly individuals. By adding an adjuvant and using cell-based vaccine production methods, the MF59-adjuvanted quadrivalent cell-based influenza vaccine (aQIVc) may boost immunogenicity and vaccine effectiveness in this population. We report the results of a randomised proof-of-concept study, investigating the immunogenicity and safety of aQIVc. Eligible participants aged ≥50 years were randomised 1: 1:1:1 to receive aQIVc (n = 116), a non-adjuvanted quadrivalent cell-based influenza vaccine (QIVc; n = 119), an MF59-adjuvanted quadrivalent egg-based influenza vaccine (aQIV; n = 116), or a high-dose quadrivalent recombinant influenza vaccine (QIVr; n = 120). The primary objective was to assess immunogenicity of aQIVc vs the comparators by haemagglutination inhibition (HI) assay 28 days post-vaccination. Secondary objectives included immunogenicity of aQIVc vs comparators 28 days and 180 post-vaccination by microneutralisation assay and 180 days post-vaccination by HI assay; and reactogenicity and safety of all study vaccines. Compared with QIVc and aQIV, aQIVc elicited a higher immune response (adjusted geometric mean titre [GMT] ratio range 1.18–1.85) against all four influenza strains at Day 29. Against QIVr, aQIVc elicited lower responses against A strains (adjusted GMT ratio range 0.79–0.84), and higher responses against B strains (adjusted GMT ratio range 1.15–1.26). Estimated GMT ratios were generally higher in the subgroup of participants aged ≥65 years vs those aged 50–64 years. aQIVc was well tolerated, eliciting similar rates of solicited local adverse events (AE) and slightly higher rates of solicited systemic AE than aQIV, and a higher rate of all solicited AE than QIVc and QIVr. No safety concern was identified. These data support further investigation of additional formulations of aQIVc in adults aged ≥50 years. Clinical trial registry:NCT04576702 •We assessed an adjuvanted, cell-based influenza vaccine (aQIVc) in adults ≥50 years•aQIVc elicited higher immune responses than a non-adjuvanted comparator•aQIVc elicited higher immune responses than an egg-based adjuvanted comparator•aQIVc showed an acceptable safety profile; no safety concerns were identified•These data are proof-of-concept for seasonal aQIVc vaccination in adults ≥50 years

• Publisher: Elsevier Ltd,Elsevier Limited
• Subject: Adjuvanted cell-derived influenza vaccine / Adjuvants / Adjuvants, Vaccine - administration & dosage / Adjuvants, Vaccine - adverse effects / Adults / Aged / Aged, 80 and over / Allergy and Immunology / Antibodies, Viral - blood / Antigens / Assaying / At risk populations / clinical trials / Comparators / Effectiveness / Eggs / elderly / Epidemics / Female / Global health / health services / hemagglutination / Hemagglutination inhibition / Hemagglutination Inhibition Tests / Humans / Immune response / Immune system / Immunogenicity / Immunogenicity, Vaccine / Influenza / influenza vaccines / Influenza Vaccines - administration & dosage / Influenza Vaccines - adverse effects / Influenza Vaccines - immunology / Influenza, Human - immunology / Influenza, Human - prevention & control / Male / MF59 adjuvant / Middle Aged / Mutation / Older people / Phase 2 / Polysorbates - administration & dosage / Polysorbates - adverse effects / Production methods / Safety / Squalene - administration & dosage / Squalene - adverse effects / Subgroups / vaccination / Vaccine Efficacy / Vaccines / Vaccines, Inactivated - administration & dosage / Vaccines, Inactivated - adverse effects / Vaccines, Inactivated - immunology / Vaccines, Subunit - administration & dosage / Vaccines, Subunit - adverse effects / Vaccines, Subunit - immunology / Viruses