Immunogenicity up to age 5 years following a single-dose or two-dose infant primary series of 10-valent or 13-valent pneumococcal conjugate vaccine each followed by a booster dose in South Africa: extended follow-up of a single-centre, open-label, non-inferiority, randomised controlled trial.

Abstract

Reduced-dosing pneumococcal conjugate vaccine (PCV) schedules (single primary dose plus booster [1+1]) are being considered and have been deployed in the UK. We aimed to evaluate the persistence of serotype-specific immunity until age 5 years in infants randomly assigned to 1+1 or two primary doses plus booster (2+1) schedules of 10-valent (PCV10) or 13-valent (PCV13) vaccine. In the original, single-centre, open-label, non-inferiority, randomised controlled trial, infants not exposed to HIV were randomly assigned (1:1:1:1:1:1) using block randomisation into the six following groups: single-dose PCV10 or PCV13 at 6 weeks (6w+1) or 14 weeks (14w+1), or two doses of PCV10 or PCV13 at 6 weeks and 14 weeks (2+1), with all receiving a 9-month booster. In this extended follow-up, serotype-specific serum IgG geometric mean concentrations (GMCs) were measured by in-house Luminex assay at age 3 years, 4 years, and 5 years. Non-inferiority was defined as the lower-bound of the 95% CI of the GMC ratio exceeding 0·5 for at least ten of the PCV13 serotypes and at least eight of the PCV10 serotypes. This follow-up study is registered at ClinicalTrials.gov (NCT04275284). In the original trial, of the 1695 who were screened, 600 children were enrolled and randomly assigned to six study groups (100 in each group) from Jan 9 to Sept 20, 2017. Of these, 354 (59%) were included in the follow-up study, including 54 from 6w+1 PCV10, 56 from 14w+1 PCV10, 64 from 2+1 PCV10, 60 from 6w+1 PCV13, 57 from 14w+1 PCV13, and 63 from the 2+1 PCV13 study groups. 986 blood samples were collected across three annual visits (349 at 3 years, 334 at 4 years, and 303 at 5 years) between Feb 18, 2020 and Aug 24, 2022. Both PCV13 1+1 schedules remained non-inferior to the PCV13 2+1 schedule up until age 5 years. Both PCV10 1+1 schedules met non-inferiority at 3 years but did not meet the non-inferiority criteria at 4 years and 5 years. Comparison of the PCV10 2+1 and PCV13 2+1 schedules demonstrated similar IgG GMCs for the ten shared serotypes up until age 5 years, with PCV13 outperforming PCV10 across most serotypes in 1+1 groups. A reduced PCV13 1+1 schedule, primed at either 6 weeks or 14 weeks, maintained non-inferior serotype-specific GMCs relative to the PCV13 2+1 schedule up until age 5 years, supporting schedule transition in countries with well established PCV programmes. The PCV10 1+1 schedules did not meet non-inferiority criteria compared with the PCV10 2+1 schedule by age 4 years. Gates Foundation and South African Medical Research Council.