- Design
- Phase 3, randomised (3:2:2), observer-blind, parallel-group multicentre trial
- Population
- 7,677 healthy adults aged 50 years or older; 7,419 in the per-protocol set
- Primary outcome
- Lot-to-lot consistency and day-29 geometric mean titre and seroconversion, aQIVc versus aQIV and versus QIVr
- Effect
- Versus aQIV: GMT ratios 1.22–1.73, all superior. Versus QIVr: non-inferior for A/H1N1 and both B strains; A/H3N2 GMT ratio 0.69 (97.5% CI 0.65–0.74), non-inferiority not met
A phase 3, observer-blind trial randomised 7,699 healthy adults aged 50 and over, 3:2:2, to an MF59-adjuvanted cell-derived higher-dose quadrivalent influenza vaccine (aQIVc; 45 μg haemagglutinin per strain with 19.5 mg squalene), the standard MF59-adjuvanted egg-derived vaccine (aQIV; 15 μg per strain), or a recombinant quadrivalent vaccine (QIVr; 45 μg per strain). Lot-to-lot consistency was met.
Against aQIV, aQIVc was superior on every strain at day 29: geometric mean titre ratios 1.53 (97.5% CI 1.43–1.64) for A/H1N1, 1.22 (1.15–1.30) for A/H3N2, 1.73 (1.63–1.85) for B/Victoria and 1.71 (1.63–1.80) for B/Yamagata, with seroconversion rate differences of 9.5 to 24.3 percentage points.
Against the recombinant vaccine the picture splits. Non-inferiority was met for A/H1N1 and both B strains, but failed for A/H3N2, where aQIVc was worse: GMT ratio 0.69 (0.65–0.74), seroconversion difference −7.4 percentage points (−10.3 to −4.6). A/H3N2 drives most severe influenza in older adults, so a vaccine that trails there is not simply a broader-dose upgrade. Reactogenicity was higher than both comparators, though mostly mild and transient, and serious adverse events were similar across arms at about 3%.
- Read the strain-level results, not the headline: this vaccine beats one comparator and loses to the other on the strain that causes most severe disease in this age group.
- Where a recombinant vaccine is available for an older adult, the H3N2 data favour it.
- Warn patients about higher local and systemic reactogenicity if aQIVc is used — most is mild and settles within days.
- Immunogenicity is a surrogate: none of these comparisons measured influenza cases or hospitalisations.
- Neither the higher-dose cell-derived nor the recombinant product is widely available in Indian practice, where the standard quadrivalent remains what most patients will actually receive.
Why it matters
A higher antigen dose is usually assumed to mean better protection, and here it did not hold for the strain that matters most.
Don't overread it
These are antibody titres, not influenza cases — no clinical protection endpoint was measured.
The statistics, in plain English
A geometric mean titre ratio above 1 means higher antibody levels; the 97.5% intervals are used because several comparisons were tested. The A/H3N2 ratio of 0.69 with an interval of 0.65 to 0.74 sits entirely below 1 and below the 0.67 non-inferiority margin at its upper edge — this is a real deficit, not an inconclusive result. What none of these numbers tells you is how many infections were prevented, because antibody titre is a surrogate for protection and an imperfect one for H3N2 in particular.
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