The two inactivated hepatitis A vaccine strains did not produce equal antibody responses

Design

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

Population

3,282 children and adolescents across four randomised cohorts, mostly Chinese

Primary outcome

seroconversion rate and geometric mean anti-HAV concentration

Effect

seroconversion at 1 month OR 3.05 (95% CI 1.88–4.96); adverse events RR 0.95 (0.76–1.20)

Inactivated hepatitis A vaccines in use worldwide are built on one of two virus strains — TZ84 or HM175 — and they are generally treated as interchangeable. This systematic review pooled seven publications arising from four randomised cohorts, 3,282 children and adolescents in total, comparing them directly. Risk of bias was assessed with the Cochrane RoB 2 tool.

TZ84-based vaccines produced higher seroconversion rates and higher geometric mean concentrations after both one and two doses. Seroconversion at one month gave an odds ratio of 3.05 (95% CI 1.88 to 4.96), and geometric mean concentration at seven months a standardised mean difference of 0.88 (0.18 to 1.58, p=0.01). Follow-up reported out to 186 months showed higher anti-HAV antibody concentrations with TZ84. Adverse events were comparable between the two (risk ratio 0.95, 0.76 to 1.20).

The authors are careful about the limits, and so should a reader be: four unique randomised cohorts, concentrated in China, heterogeneous, and every outcome a surrogate for protection rather than protection itself. Hepatitis A vaccination in Indian practice is largely private and the product chosen is often whatever the clinic stocks. This is a reason to know which strain that is and to record it, not a reason to tell a family that a previously given vaccine was the wrong one.

• Find out which strain the hepatitis A vaccine in your fridge is based on — it is on the product information, not the schedule
• Record the product name in the immunisation record, not just the date
• Do not re-vaccinate a child who completed a course with the other strain on the basis of this analysis
• Both products had comparable adverse event rates, so safety is not the deciding factor
• Remember that in high-endemicity settings many children are already immune from natural infection

Why it matters

Two vaccines treated as equivalent in practice turn out to differ on the endpoint their licences were granted on.

Don't overread it

Every outcome here is an antibody measurement — no study compared rates of hepatitis A disease between the two vaccines.

The statistics, in plain English

An odds ratio of 3.05 for seroconversion sounds decisive, but seroconversion rates for both vaccines are high, and a ratio computed on a near-ceiling outcome magnifies a small absolute gap. The standardised mean difference of 0.88 with an interval running from 0.18 to 1.58 is wide, which is what four heterogeneous cohorts produce. Most importantly, antibody concentration is a surrogate: it correlates with protection but the threshold that matters clinically is not established by this analysis.

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