A one-dose pneumococcal primary series holds to age 5 - but only with the 13-valent vaccine

Design

Extended follow-up of a single-centre, open-label, non-inferiority randomised controlled trial, South Africa

Population

354 of 600 originally randomised children not exposed to HIV, sampled at ages 3, 4 and 5

Primary outcome

Serotype-specific serum IgG geometric mean concentrations, non-inferiority of 1+1 versus 2+1

Effect

13-valent 1+1 non-inferior to 2+1 at both priming ages to age 5; 10-valent 1+1 met non-inferiority at 3 years but not at 4 or 5 years

Six hundred South African infants not exposed to HIV were randomised in 2017 into six groups: a single primary dose of 10-valent or 13-valent pneumococcal conjugate vaccine at either 6 or 14 weeks, or two primary doses at 6 and 14 weeks, all with a 9-month booster. This extended follow-up measured serotype-specific IgG at ages 3, 4 and 5 in 354 of them, across 986 blood samples.

Both 13-valent single-dose schedules stayed non-inferior to the two-dose schedule all the way to age 5, whether primed at 6 weeks or 14 weeks. The 10-valent single-dose schedules met the non-inferiority criterion at age 3 but failed it at ages 4 and 5. Where two primary doses were given, the two vaccines produced similar concentrations for their ten shared serotypes; the difference between products appeared only in the reduced schedules.

This matters wherever a programme is weighing dropping a dose, which is a real fiscal question in India as elsewhere. Two cautions attach. The outcome is immunogenicity, a surrogate: antibody concentrations above a threshold are not the same as demonstrated protection against invasive disease, particularly against carriage and herd effects. And the finding is product-specific in a way that is easy to lose in translation - a country running a 1+1 schedule needs to know which conjugate vaccine its programme actually buys, because the answer here differs by product from age 4 onwards.

• Check which pneumococcal conjugate product a programme uses before applying any 1+1 evidence to it.
• Note that the finding is antibody persistence, not proven protection against invasive disease.
• Priming at 6 weeks and at 14 weeks performed equally in the 13-valent groups.
• The two vaccines performed similarly when two primary doses were given; the gap opens only with one.
• This cohort excluded HIV-exposed infants, which limits transfer to high-prevalence settings.

The statistics, in plain English

Non-inferiority here required the lower bound of the 95 per cent confidence interval of the geometric mean concentration ratio to exceed 0.5 for at least ten of thirteen serotypes, which is a permissive margin - it allows antibody concentrations to be up to half those of the comparator. Only 354 of the original 600 children returned, and differential loss to follow-up over five years can bias either way. Geometric mean concentration is a surrogate endpoint; no clinical outcomes were measured.

Read the rest in the app

You have read your two free briefings this month. The app carries all 27 specialties, every morning, free — and this finding is waiting in it.

Get Daily Doctor — free

Scan to keep reading on your phone. No account needed to start.