Recombinant influenza vaccine in severe obesity: better titres, briefly

Design

open-label randomised clinical trial across 15 French centres, six months of follow-up

Population

206 adults with body mass index 35 kg/m2 or above; median BMI 41.0, median age 50, 60.2% women

Primary outcome

ratio of geometric mean haemagglutination-inhibition titres, recombinant versus standard-dose, at day 28

Effect

A/H1N1 1.6 (95% CI 1.1-2.3), A/H3N2 2.0 (1.3-3.2), B/Yamagata 1.3 (1.0-1.8), B/Victoria 0.9 (0.6-1.3); no difference at day 180

Severe obesity raises the risk of severe influenza and blunts the antibody response to vaccination. The FLUO trial randomised 206 French adults with a body mass index of 35 or more, 1:1 and open-label across 15 centres, to a recombinant influenza vaccine or an egg-based standard-dose vaccine, with haemagglutination-inhibition titres at day 28 as the primary outcome.

At day 28 the geometric mean titre ratio favoured the recombinant vaccine for A/H1N1 (1.6, 95% CI 1.1-2.3), A/H3N2 (2.0, 1.3-3.2) and B/Yamagata (1.3, 1.0-1.8), but not B/Victoria (0.9, 0.6-1.3). The advantage did not vary by age or by degree of obesity. By day 180 the titres no longer differed. Reactogenicity and safety were similar.

Two things constrain what this means. Antibody titre is an immunological surrogate, not influenza; no clinical outcomes were measured, and 206 patients could not have measured them. And the difference had disappeared by six months, which is most of a flu season. So this supports preferring a recombinant vaccine where one is available and affordable for a patient with severe obesity, without promising fewer infections. In India, recombinant influenza vaccine is not generally available, and the practical action remains the one that is under-done: vaccinating this group at all.

• Vaccinate patients with severe obesity against influenza — coverage, not product, is the bigger gap
• Where a recombinant vaccine is available and affordable, it is a reasonable preference in this group
• Do not promise fewer infections: the trial measured antibody titres, not illness
• The advantage had gone by six months, which matters across a full season
• Recombinant influenza vaccine is not generally available in India; use what is

The statistics, in plain English

A geometric mean titre ratio of 2.0 means twice the antibody level, not twice the protection — the relationship between titre and protection is non-linear and strain-dependent. Two of the three positive intervals come close to 1.0 at the lower bound (1.1 for H1N1, 1.0 for B/Yamagata), so those results are marginal, and the fourth strain showed nothing. With four strains tested, one non-significant result is unsurprising. The open-label design does not much affect an antibody measurement, but it does affect reported reactogenicity.

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