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Summary Background Data are scarce from low-income and middle-income countries (LMICs) to support the choice of vaccination schedule for the introduction of pneumococcal conjugate vaccines (PCV). We aimed to compare the immunogenicity of four different infant PCV10 schedules in infants in Vietnam. Methods In this single-blind, parallel-group, open-label, randomised controlled trial, infants aged 2 months were recruited by community health staff in districts 4 and 7 of Ho Chi Minh City, Vietnam. Eligible infants had no clinically significant maternal or prenatal history and were born at or after 36 weeks' gestation. Participants were randomly assigned (3:3:5:4:5:4) using block randomisation, stratified by district, to one of six PCV10 or PCV13 vaccination schedules. Here we report results for four groups: group A, who were given PCV10 at ages 2, 3, 4, and 9 months (a 3 + 1 schedule); group B, who were vaccinated at ages 2, 3, and 4 months (3 + 0 schedule); group C, who were vaccinated at ages 2, 4, and 9·5 months (2 + 1 schedule); and group D, who were vaccinated at ages 2 and 6 months (two-dose schedule). Laboratory-based assessors were masked to group allocation. Blood samples were collected at different prespecified timepoints between ages 3–18 months depending on group allocation, within 27–43 days after vaccination, and these were analysed for serotype-specific IgG and opsonophagocytic responses. Participants were followed-up until age 24 months. The primary outcome was the proportion of infants with serotype-specific IgG levels of 0·35 μg/mL or higher at age 5 months, analysed as a non-inferiority comparison (10% margin) of the two-dose and three-dose primary series (group C vs groups A and B combined). We also compared responses 4 weeks after two doses administered at either ages 2 and 4 months (group C) or at ages 2 and 6 months (group D). The primary endpoint was analysed in the per-protocol population. Reactogenicity has been reported previously. This study is registered with ClinicalTrials.gov , NCT01953510 , and is now closed to accrual. Findings Between Sept 30, 2013, and Jan 9, 2015, 1201 infants were enrolled and randomly assigned to group A (n=152), group B (n=149), group C (n=250), group D (n=202), or groups E (n=251) and F (n=197). In groups A–D, 388 (52%) of 753 participants were female and 365 (48%) were male. 286 (95%) participants in groups A and B combined (three-dose primary series) and 237 (95%) in group C (two-dose primary series) completed the primary vaccination series and had blood samples taken within the specified time window at age 5 months (per-protocol population). At this timepoint, a two-dose primary series was non-inferior to a three-dose primary series for eight of ten vaccine serotypes; exceptions were 6B (84·6% [95% CI 79·9–88·6] of infants had protective IgG concentrations after three doses [groups A and B combined] vs 76·8% [70·9–82·0] of infants after two doses [group C]; risk difference 7·8% [90% CI 2·1–13·6]) and 23F (90·6% [95% CI 86·6–93·7] vs 77·6% [71·8–82·2]; 12·9% [90% CI 7·7–18·3]). Two doses at ages 2 and 6 months produced higher antibody levels than two doses at ages 2 and 4 months for all serotypes except 5 and 7F. Interpretation A two-dose primary vaccination series was non-inferior to a three-dose primary vaccination series while two doses given with a wider interval between doses increased immunogenicity. The use of a two-dose primary vaccination schedule using a wider interval could be considered in LMIC settings to extend protection in the second year of life. Funding Australian National Health and Medical Research Council, and The Bill & Melinda Gates Foundation.

Highlights • 1st study to directly compare effect of 2+1 schedule of PCV10 or PCV13 on carriage. • Includes an unvaccinated comparator group. • Both PCVs reduce carriage of serotypes in the corresponding vaccine. • May be some differences between the vaccines in their impact on carriage. • Majority of carriage was vaccine-type, so both vaccines likely to be beneficial., Background Pneumococcal conjugate vaccines (PCVs) generate herd protection by reducing nasopharyngeal (NP) carriage. Two PCVs, PCV10 and PCV13, have been in use for over a decade, yet there are few data comparing their impact on carriage. Here we report their effect on carriage in a 2+1 schedule, compared with each other and with unvaccinated controls. Methods Data from four groups within a parallel, open-label randomised controlled trial in Ho Chi Minh City contribute to this article. Three groups were randomised to receive a 2+1 schedule of PCV10 (n = 250), a 2+1 schedule of PCV13 (n = 251), or two doses of PCV10 at 18 and 24 months (controls, n = 197). An additional group (n = 199) was recruited at 18 months to serve as controls from 18 to 24 months. NP swabs collected at 2, 6, 9, 12, 18, and 24 months were analysed (blinded) for pneumococcal carriage. This study aimed to determine if PCV10 and PCV13 have a differential effect on pneumococcal carriage, a secondary outcome of the trial. We also describe the serotype distribution among unvaccinated participants. Trial registration: ClinicalTrials.gov NCT01953510. Findings Compared with unvaccinated controls, a 2+1 schedule of PCV10 reduced PCV10-type carriage by 45–62% from pre-booster through to 24 months of age, and a 2+1 schedule of PCV13 reduced PCV13-type carriage by 36–49% at 12 and 18 months of age. Compared directly with each other, there were few differences between the vaccines in their impact on carriage. Vaccine serotypes accounted for the majority of carriage in unvaccinated participants. Interpretation Both PCV10 and PCV13 reduce the carriage of pneumococcal vaccine serotypes. The introduction of either vaccine would have the potential to generate significant herd protection in this population. Funding National Health and Medical Research Council of Australia, Bill & Melinda Gates Foundation.

Background: This study investigated the immunogenicity and impact on nasopharyngeal carriage of a single dose of PCV10 given to 18-month-old Vietnamese children. This information is important for countries considering catch-up vaccination during PCV introduction and in the context of vaccination during humanitarian crises. Methods: Two groups of PCV-naïve children within the Vietnam Pneumococcal Project received PCV10 (n=197) or no PCV (unvaccinated; n=199) at 18 months of age. Blood samples were collected at 18, 19, and 24 months of age, and nasopharyngeal swabs at 18 and 24 months of age. Immunogenicity was assessed by measuring serotype-specific IgG, opsonophagocytosis (OPA) and memory B cells (Bmem). Pneumococci were detected and quantified using real-time PCR and serotyped by microarray. Findings: At 19 months of age, IgG and OPA responses were higher in the PCV10 group compared with the unvaccinated group for all PCV10 serotypes and cross-reactive serotypes 6A and 19A. This was sustained out to 24 months of age, at which point PCV10-type carriage was 60% lower in the PCV10 group than the unvaccinated group. Bmem levels increased between 18 and 24 months of age in the vaccinated group. Interpretation: We demonstrate strong protective immune responses in vaccinees following a single dose of PCV10 at 18 months of age, and a potential impact on herd protection through a substantial reduction in vaccine-type carriage. A single dose of PCV10 in the second year of life could be considered as part of catch-up campaigns or in humanitarian crises to protect children at high-risk of pneumococcal disease. publishedVersion