A higher-dose adjuvanted cell-based flu vaccine beat the adjuvanted egg vaccine, and lost to recombinant on H3N2

Design

phase 3, randomised, observer-blind, parallel-group multicentre trial, 3:2:2 allocation

Population

7,677 healthy adults aged 50 years or older

Primary outcome

day-29 geometric mean titre ratios and seroconversion rate differences, plus lot-to-lot consistency

Effect

versus adjuvanted egg vaccine, GMT ratios 1.22-1.73 across strains; versus recombinant, 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 adults aged 50 or over, 3:2:2, to an MF59-adjuvanted cell-derived higher-dose quadrivalent vaccine (45 micrograms of haemagglutinin per strain), the standard MF59-adjuvanted egg-derived vaccine (15 micrograms), or recombinant quadrivalent vaccine (45 micrograms). Lot-to-lot consistency was met.

Against the adjuvanted egg vaccine, the new formulation was both non-inferior and superior on all four strains at day 29: geometric mean titre ratios of 1.53 for A/H1N1, 1.22 for A/H3N2, 1.73 for B/Victoria and 1.71 for B/Yamagata, with seroconversion differences of 9.5 to 24.3 percentage points. Against recombinant vaccine the picture splits. Non-inferiority was met for A/H1N1 and both B strains, but not for A/H3N2, where the titre ratio was 0.69 (97.5% CI 0.65 to 0.74) and the seroconversion difference was 7.4 percentage points against it.

H3N2 is the strain that drives severe seasons in older adults, so a formulation that is better than one comparator and worse than another on precisely that strain does not have a simple answer. Local and systemic reactions were commoner with the higher-dose adjuvanted product, though mild and transient. None of these products dominates Indian practice, where trivalent and quadrivalent egg-based vaccines remain the norm and uptake, not formulation, is the binding constraint.

• Read immunogenicity comparisons strain by strain - this one reverses direction between H3N2 and the B strains
• Expect more local and systemic reactogenicity with higher-dose adjuvanted formulations, and warn patients
• In older adults, H3N2 is the strain that matters most for severe outcomes
• Do not translate titre ratios into expected efficacy; no clinical endpoint was measured here
• Uptake remains the larger lever in Indian practice than choice between formulations

Why it matters

It shows the choice between modern influenza vaccine platforms is strain-specific rather than a single ranking.

Don't overread it

These are antibody endpoints - no influenza infection, hospitalisation or death outcome was measured.

The statistics, in plain English

A geometric mean titre ratio of 0.69 means antibody titres were about 31% lower than with recombinant vaccine, and the 97.5% interval of 0.65 to 0.74 sits entirely below the 0.67 non-inferiority margin's favourable side - a clear miss, not a borderline one. Superiority over the adjuvanted egg vaccine is genuine but measured in antibody, and the relationship between titre and protection in older adults is imperfect. Trials of this size detect small immunological differences reliably and say nothing about whether they translate into fewer hospital admissions.

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