Two hepatitis A vaccine strains compared, on antibody levels rather than disease

Design

systematic review and meta-analysis of randomised cohorts, Cochrane RoB 2 assessed

Population

3282 children and adolescents across four randomised cohorts, seven publications

Primary outcome

seroconversion rate and geometric mean antibody concentration

Effect

seroconversion at 1 month odds ratio 3.05 (95% CI 1.88-4.96); adverse events comparable (RR 0.95, 0.76-1.20)

Seven publications from four randomised paediatric cohorts, 3282 children and adolescents in total, were pooled to compare two inactivated hepatitis A vaccine strains on immunogenicity and safety. Seroconversion at one month favoured the TZ84-based vaccines (odds ratio 3.05, 95% CI 1.88 to 4.96), as did geometric mean concentrations at seven months (standardised mean difference 0.88, 95% CI 0.18 to 1.58, p = 0.01). Follow-up extending to 186 months showed higher reported antibody concentrations with the same strain. Adverse events were comparable (risk ratio 0.95, 95% CI 0.76 to 1.20).

The limitations the authors list are the ones that decide how to read it. Four unique randomised cohorts is a thin evidence base for a pooled estimate, the studies are geographically concentrated in one country, heterogeneity was substantial, and every outcome is a surrogate. Nobody in these trials was followed for hepatitis A.

That last point governs the clinical reading. Both vaccines produce protective antibody in the great majority of children, and hepatitis A vaccination is highly effective in practice; a difference in antibody titre between two effective vaccines is not the same as a difference in disease prevented. For Indian practice, where hepatitis A remains endemic and vaccination is increasingly used in children with chronic liver disease, availability and cost are the operative considerations, not this titre gap.

• Both strains produce seroconversion in the large majority of children - neither is ineffective.
• Treat higher antibody titre as a surrogate; no clinical hepatitis A outcomes were compared.
• Do not switch an established vaccination programme on this evidence.
• Note the geographic concentration of the trials when generalising.
• In children with chronic liver disease, the priority remains that they are vaccinated at all, with whichever product is available.

Why it matters

It is a reminder that comparative vaccine immunogenicity data answer a different question from comparative effectiveness.

Don't overread it

These are surrogate immunogenicity outcomes from four cohorts in one region; no difference in hepatitis A disease has been shown.

The statistics, in plain English

A standardised mean difference of 0.88 is a large effect in antibody concentration, and the confidence interval (0.18 to 1.58) stays above zero - so the titre difference is real. But titre is a surrogate endpoint, and above the protective threshold, more antibody does not straightforwardly mean more protection. With only four unique randomised cohorts, the pooled estimate also rests on very few independent comparisons, whatever the total participant count suggests.

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