Abstract
SummaryBackgroundFew data are available to support the choice between the two currently available pneumococcal conjugate vaccines (PCVs), ten-valent PCV (PCV10) and 13-valent PCV (PCV13). Here we report a head-to-head comparison of the immunogenicity and reactogenicity of PCV10 and PCV13.MethodsIn this parallel, open-label, randomised controlled trial, healthy infants from two districts in Ho Chi Minh City, Vietnam, were randomly allocated (in a 3:3:5:4:5:4 ratio), with use of a computer-generated list, to one of six infant PCV schedules: PCV10 in a 3 + 1 (group A), 3 + 0 (group B), 2 + 1 (group C), or two-dose schedule (group D); PCV13 in a 2 + 1 schedule (group E); or no infant PCV (control; group F). Blood samples were collected from infants between 2 months and 18 months of age at various timepoints before and after PCV doses and analysed (in a blinded manner) by ELISA and opsonophagocytic assay. The trial had two independent aims: to compare vaccination responses between PCV10 and PCV13, and to evaluate different schedules of PCV10. In this Article, we present results pertaining to the first aim. The primary outcome was the proportion of infants with an IgG concentration of at least 0·35 μg/mL for the ten serotypes common to the two vaccines at age 5 months, 4 weeks after the two-dose primary vaccination series (group C vs group E, per protocol population). An overall difference among the schedules was defined as at least seven of ten serotypes differing in the same direction at the 10% level. We also assessed whether the two-dose primary series of PCV13 (group E) was non-inferior at the 10% level to a three-dose primary series of PCV10 (groups A and B). This trial is registered with ClinicalTrials.gov, number NCT01953510.FindingsOf 1424 infants screened between Sept 30, 2013, and Jan 9, 2015, 1201 were allocated to the six groups: 152 (13%) to group A, 149 (12%) to group B, 250 (21%) to group C, 202 (17%) to group D, 251 (21%) to group E, and 197 (16%) to group F. 237 (95%) participants in group C (PCV10) and 232 (92%) in group E (PCV13) completed the primary vaccination series and had blood draws within the specified window at age 5 months, at which time the proportion of infants with IgG concentrations of at least 0·35 μg/mL did not differ between groups at the 10% level for any serotype (PCV10–PCV13 risk difference −2·1% [95% CI −4·8 to −0·1] for serotype 1; −1·3% [–3·7 to 0·6] for serotype 4; −3·4% [–6·8 to −0·4] for serotype 5; 15·6 [7·2 to 23·7] for serotype 6B; −1·3% [–3·7 to 0·6] for serotype 7F; −1·6% [–5·1 to 1·7] for serotype 9V; 0·0% [–2·7 to 2·9] for serotype 14; −2·1% [–5·3 to 0·9] for serotype 18C; 0·0% [–2·2 to 2·3] for serotype 19F; and −11·6% [–18·2 to −4·9] for serotype 23F). At the same timepoint, two doses of PCV13 were non-inferior to three doses of PCV10 for nine of the ten shared serotypes (excluding 6B). Reactogenicity and serious adverse events were monitored according to good clinical practice guidelines, and the profiles were similar in the two groups.InterpretationPCV10 and PCV13 are similarly highly immunogenic when used in 2 + 1 schedule. The choice of vaccine might be influenced by factors such as the comparative magnitude of the antibody responses, price, and the relative importance of different serotypes in different settings.FundingNational Health and Medical Research Council of Australia, and Bill & Melinda Gates Foundation.
Highlights
Streptococcus pneumoniae is a leading vaccine-preventable cause of serious infection in young children, and was estimated to cause 294 000 deaths among children younger than 5 years of age in 2015.1 The greatest burden of pneumococcal disease and related mortality is in low-income and middle-income countries (LMICs)
The protocol was approved by the Institutional Review Board at the Pasteur Institute of Ho Chi Minh City, Vietnam, and ethical approval was obtained from the Human Research Ethics Committee of the Northern Territory Department of Health and Menzies School of Health Research, Australia, and the Ministry of Health Ethics Committee, Vietnam
We showed that two doses of PCV13 were noninferior to three doses of PCV10 in terms of the proportion of infants with protective serotype-specific IgG concentrations, with the upper bound of the CI for the between-group difference less than 10% for nine of the ten shared serotypes
Summary
Streptococcus pneumoniae (pneumococcus) is a leading vaccine-preventable cause of serious infection in young children, and was estimated to cause 294 000 deaths among children younger than 5 years of age in 2015.1 The greatest burden of pneumococcal disease and related mortality is in low-income and middle-income countries (LMICs).Two pneumococcal conjugate vaccines (PCVs) are currently licensed for infant vaccination against pneumo coccus. 13-valent PCV (PCV13) contains pneumococcal serotypes 1, 3, 4, 5, 6A, 6B, 7F, 9V, 14, 18C, 19A, 19F, and 23F. Ten-valent PCV (PCV10) contains ten of these serotypes (except serotypes 3, 6A, and 19A), there is evidence for some crossprotection against serotype 6A and 19A disease.[2,3,4] PCV10 and PCV13 have been shown to be immunologically non-inferior to the first-licensed, seven-valent PCV (PCV7),[5,6,7] but there are few data directly comparing. Evidence before this study The licensure of the two currently available pneumococcal conjugate vaccines (PCVs), the ten-valent PCV (PCV10) and the 13-valent PCV (PCV13), was based on demonstration of their immunological non-inferiority to seven-valent PCV. A further two European trials of investigational vaccines contained control groups that received PCV10 or PCV13 in a 3 + 1 schedule. These studies indicated that both vaccines are highly immunogenic. Given the paucity of comparative data on PCV10 and PCV13, countries considering PCV introduction have little on which to base their decision, other than the relative cost of the vaccines
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