Abstract
SummaryBackgroundRoutine childhood immunisation with pneumococcal conjugate vaccine (PCV) has changed the epidemiology of pneumococcal disease across age groups, providing an opportunity to reconsider PCV dosing schedules. We aimed to evaluate the post-booster dose immunogenicity of ten-valent (PCV10) and 13-valent (PCV13) PCVs between infants randomly assigned to receive a single-dose compared with a two-dose primary series.MethodsWe did an open-label, non-inferiority, randomised study in HIV-unexposed infants at a single centre in Soweto, South Africa. Infants were randomly assigned to receive one priming dose of PCV10 or PCV13 at ages 6 weeks (6w + 1 PCV10 and 6w + 1 PCV13 groups) or 14 weeks (14w + 1 PCV10 and 14w + 1 PCV13 groups) or two priming doses of PCV10 or PCV13, one each at ages 6 weeks and 14 weeks (2 + 1 PCV10 and 2 + 1 PCV13 groups); all participants then received a booster dose of PCV10 or PCV13 at 40 weeks of age. The primary endpoint was geometric mean concentrations (GMCs) of serotype-specific IgG 1 month after the booster dose, which was assessed in all participants who received PCV10 or PCV13 as per the assigned randomisation group and for whom laboratory results were available at that timepoint. The 1 + 1 vaccine schedule was considered non-inferior to the 2 + 1 vaccine schedule if the lower bound of the 96% CI for the GMC ratio was greater than 0·5 for at least ten PCV13 serotypes and eight PCV10 serotypes. Safety was a secondary endpoint. This trial is registered with ClinicalTrials.gov (NCT02943902) and is ongoing.FindingsOf 1695 children assessed, 600 were enrolled and randomly assigned to one of the six groups between Jan 9 and Sept 20, 2017; 542 were included in the final analysis of the primary endpoint (86–93 per group). For both PCV13 and PCV10, a 1+1 dosing schedule (either beginning at 6 or 14 weeks) was non-inferior to a 2 + 1 schedule. For PCV13, the lower limit of the 96% CI for the ratio of GMCs between the 1 + 1 and 2 + 1 groups was higher than 0·5 for ten serotypes in the 6w+1 group (excluding 6B, 14, and 23F) and 11 serotypes in the 14w + 1 group (excluding 6B and 23F). For PCV10, the lower limit of the 96% CI for the ratio of GMCs was higher than 0·5 for all ten serotypes in the 6w+1 and 14w + 1 groups. 84 serious adverse events were reported in 72 (12%) of 600 participants. 15 occurred within 28 days of vaccination, but none were considered to be related to PCV injection. There were no cases of culture-confirmed invasive pneumococcal disease.InterpretationThe non-inferiority in post-booster immune responses following a single-dose compared with a two-dose primary series of PCV13 or PCV10 indicates the potential for reducing PCV dosing schedules from a 2 + 1 to 1 + 1 series in low-income and middle-income settings with well established PCV immunisation programmes.FundingThe Bill & Melinda Gates Foundation (OPP1 + 152352).
Highlights
We identified a single previous study on PCV13 from the UK, which reported that serotype-specific IgG geometric mean concentrations (GMCs) following a booster dose of PCV13 at age 12 months were non-inferior in children who received a single priming (1 + 1) dose at age 3 months compared with those vaccinated with a two-dose primary series at ages 2 and 4 months (2 + 1)
For PCV13, we show that delaying the first dose in the 1 + 1 schedule to 14 weeks was associated with higher post-first dose GMCs and a higher percentage of children with serotype-specific antibody concentrations above the putative correlate of protection for invasive pneumococcal diseases
Post-booster IgG GMCs were higher in the 6w + 1 PCV13 group than in the 2 + 1 PCV13 group for serotypes 1, 3, 4, 19A, and 19F, and lower in the 6w+1 PCV13 group than in the 2 + 1 PCV13 group for serotypes 6B and 23F
Summary
WHO recommends immunisation of children with tenvalent (PCV10) or 13-valent (PCV13) pneumococcal conjugate vaccine (PCV), with either three doses given during early infancy or two doses given in early infancy and a booster dose given from age 9 months onward (so-called 2 + 1 schedule). both PCV dosing schedules and valencies are effective in preventing invasive pneumococcal disease caused by vaccine serotypes, the absence of a booster dose has been associated with waning immunity.3–5As well as preventing vaccine-type disease, PCV immunisation of infants reduces the risk of nasopharyngeal acquisition of Streptococcus pneumoniae serotypes included in the vaccine. a correlate of protection against pneumococcal colonisation has not been definitively established, a meta-analysis of PCV10related studies observed an inverse association between www.thelancet.com/infection Vol 20 December 2020Research in contextEvidence before this study Routine immunisation of children with pneumococcal conjugate vaccine (PCV) has resulted in major changes in the epidemiology of pneumococcal disease among the age group targeted for vaccination, as well as among those not targeted (through an indirect effect). WHO recommends immunisation of children with tenvalent (PCV10) or 13-valent (PCV13) pneumococcal conjugate vaccine (PCV), with either three doses given during early infancy or two doses given in early infancy and a booster dose given from age 9 months onward (so-called 2 + 1 schedule).. WHO recommends immunisation of children with tenvalent (PCV10) or 13-valent (PCV13) pneumococcal conjugate vaccine (PCV), with either three doses given during early infancy or two doses given in early infancy and a booster dose given from age 9 months onward (so-called 2 + 1 schedule).1 Both PCV dosing schedules and valencies are effective in preventing invasive pneumococcal disease caused by vaccine serotypes, the absence of a booster dose has been associated with waning immunity.. The study concluded that post-booster immune responses in infants primed with a single dose of PCV13 were equivalent or superior (for serotypes 1, 4, 14, and 19F) to those primed with two doses of PCV, except for serotypes 6B and 23F
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