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Two-Dose PCV10 Schedule Sustains Non-Inferiority Over Five-and-a-Half Years in Viet Nam
A long-term follow-up of a cluster-randomised trial found that the reduced two-dose 1p+1 PCV10 schedule remained non-inferior to standard three-dose regimens for vaccine-type nasopharyngeal carriage at 5.5 years, with differences in infants of -1.2 percentage points versus the 2p+1 schedule (95% CI -3.0 to 0.6) and -0.2 percentage points versus the 3p+0 schedule (95% CI -1.7 to 1.4). Notably, the same magnitude of decline in vaccine-type carriage was observed in unvaccinated adult caregivers across all intervention groups, indicating that reduced-dose schedules can generate population-level indirect protection comparable to standard regimens.
What Was Studied
This study examined whether a reduced two-dose PCV10 schedule (1p+1: doses at ages 2 and 12 months) could sustain non-inferiority to standard three-dose schedules for the prevalence of vaccine-type nasopharyngeal carriage in infants and toddlers at 5.5 years after vaccine introduction, and whether reduced schedules generated indirect protection in unvaccinated age groups such as adult caregivers and preschool children.
How It Was Studied
This was a long-term follow-up of a cluster-randomised controlled trial conducted across 24 communes in Nha Trang, Viet Nam, with an additional three unvaccinated communes serving as observational comparators. A total of 49,644 participants were enrolled across four age groups: infants (aged 4–11 months), toddlers (aged 14–24 months), preschool children (aged 3–4 years), and adult caregivers. Communes were assigned in equal proportions to one of four PCV10 infant vaccination schedules — 0p+1, 1p+1, 2p+1, or 3p+0 — and vaccine-type carriage prevalence was assessed at multiple time points from 2016 through 2022. Non-inferiority was defined as the upper bound of the 95% confidence interval for the difference in vaccine-type carriage prevalence not exceeding 5 percentage points.
What Was Observed
- The 1p+1 schedule met the pre-specified non-inferiority threshold against both standard three-dose comparators in infants and toddlers at 5.5 years. Absolute carriage prevalence was low across all groups: 0.7% in 1p+1 infants versus 1.9% in 2p+1 and 0.9% in 3p+0, with differences well within the 5 percentage point margin.
- The proportion of pneumococcal carriers harbouring PCV10-type serotypes fell sharply over the trial period in infants (from 52.1% to 7.6%) and in toddlers (from 50.0% to 4.0%), reflecting a sustained and substantial reduction in vaccine-type carriage across vaccinated age groups.
- Indirect protection was observed in unvaccinated adult caregivers, among whom the proportion carrying PCV10-type serotypes declined from 39.4% to 10.5% — a trajectory that closely mirrored the decline seen in vaccinated children, and was consistent across all intervention arms regardless of dose number.
- The single-dose 0p+1 schedule met non-inferiority criteria in seven of eight intention-to-treat comparisons, suggesting that even a single dose may be sufficient to contribute to programme-level herd protection under certain conditions, though this remains a secondary finding.
Why This Matters
The results demonstrate that a simplified two-dose PCV10 schedule can maintain population-level control of vaccine-type pneumococcal carriage over a sustained period without sacrificing the indirect protection that benefits unvaccinated individuals. As the authors note, this has direct relevance for vaccine programme efficiency: a reduced-dose schedule lowers both programmatic costs and delivery complexity, which could ease implementation in resource-constrained settings where maintaining three-dose coverage remains logistically challenging.
How to Read This Result
This is a high-quality, large-scale randomised trial with long follow-up, and the non-inferiority findings are robust; however, the results are most applicable to settings that have already established a PCV programme with a prior catch-up campaign, and the observed carriage declines may partly reflect durable herd immunity from that initial campaign rather than the ongoing reduced schedule alone.
Limitations
Generalisability is explicitly restricted to settings where a pneumococcal conjugate vaccine programme is already established and a catch-up campaign has been conducted; the findings may not transfer directly to programmes launching without this foundation. The long follow-up design introduces the possibility of temporal confounding, as other factors influencing carriage prevalence could have changed over the 5.5-year period. Additionally, the unvaccinated communes served only as observational comparators and were not randomised, which limits the strength of conclusions drawn from direct comparisons with that group.