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The aim was to identify an appropriate infant pneumococcal vaccination strategy for resource poor countries. Fijian infants received zero, one, two, or three doses of 7-valent pneumococcal conjugate vaccine (PCV) in early infancy. Following three PCV doses, geometric mean concentration (GMC) to all seven serotypes were ≥1.0 μg/mL, and >85% of children achieved antibody levels ≥0.35 μg/mL at 18 weeks. Following two doses, GMC were lower for 6B, 14, and 23F, but higher for 19F compared with three doses. Following a single dose, significant responses were seen for all serotypes post-primary series compared with the unvaccinated. By 12 months, differences between two and three doses persisted for serotype 14 only. Although GMC following three doses are higher than after two doses, the differences were small. A single dose may offer some protection for most serotypes.

To evaluate the immunological impact of the 23-valent pneumococcal polysaccharide vaccine (23vPPS) at 12 months, for children who have received zero to three infant doses of seven-valent pneumococcal conjugate vaccine (PCV), on responses to a subsequent exposure to a small dose of 23vPPS (mPPS). Five hundred and fifty-two Fijian infants were stratified by ethnicity and randomized into eight groups to receive zero, one, two, or three PCV doses at 14 weeks, six and 14 weeks, or six, ten, and 14 weeks. Within each group, half received 23vPPS at 12 months and all received mPPS at 17 months. Sera were taken prior and one month post-mPPS. By 17 months, geometric mean antibody concentrations (GMC) to all 23 serotypes in 23vPPS were significantly higher in children who had received 23vPPS at 12 months compared to those who had not. Post-mPPS, children who had not received the 12 month 23vPPS had a significantly higher GMC for all PCV serotypes compared with those who had (each p < 0.02). For the non-PCV serotypes, children who had not received the 12 month 23vPPS had significantly higher GMC for six of 16 non-PCV serotypes (7F, 9N, 12F, 19A, 22F, 33F) than those who did (each p < 0.02). After adjusting for the pre-mPPS level, exposure to 23vPPS was associated with a lower response to mPPS for all serotypes (each p < 0.001). Despite higher antibody concentrations at 17 months in children who had received 23vPPS at 12 months, the response to a re-challenge was poor for all 23 serotypes compared to children who had not received the 12 month 23vPPS.

•We achieved our intended sample size of 210 participants.•Rates of ear disease (71%) and 23vPPV-type carriage (26%) were lower than expected.•We were unable to show maternal 23vPPV efficacy against infant ear disease or 23vPPV-type carriage.•23vPPV in pregnancy halved infant ear disease concurrent with 23vPPV-type carriage.•23vPPV in pregnancy may complement childhood pneumococcal vaccination programs. We assessed maternal 23-valent pneumococcal polysaccharide (23vPPV) vaccine efficacy (VE) against middle ear disease and pneumococcal carriage amongst Australian Indigenous infants. In an open label, allocation concealed, outcome-assessor blinded, community stratified, randomised controlled trial, healthy pregnant Indigenous women aged 17–39 years in the Northern Territory of Australia received the 23vPPV (1:1:1) at: 30–36 weeks gestation, birth, or were unvaccinated (ClinicalTrials.gov NCT00714064). Co-primary outcomes were the point prevalences of infant middle ear disease and 23vPPV-type carriage at age 7 months. The consent rate was 50% (313/632). Among 227 eligible participants randomised, retention rates were 86% (66/77) controls; 89% (67/75) pregnancy vaccinees; 88% (66/75) birth vaccinees. At infant age 7 months, ear disease prevalence was: 71% (47/66) controls, 63% (42/67) pregnancy vaccinees, 76% (50/66) birth vaccinees; and 23vPPV-type carriage was: 26% (17/66) controls, 18% (12/67) pregnancy vaccinees, 18% (12/66) birth vaccinees. For pregnancy vaccinees, VE was 12% (95% CI −12% to 31%) against infant ear disease and 30% (95% CI −34% to 64%) against 23vPPV-type carriage. In a post-hoc analysis, VE against infant ear disease concurrent with carriage of 23vPPV or related types was 51% (95% CI −2% to 76%). There were no serious adverse effects following receipt of the 23vPPV in pregnancy or at birth. In a high risk population, our study was unable to demonstrate efficacy of 23vPPV in pregnancy against the co-primary outcomes of either all-cause infant ear disease or 23vPPV-type nasopharyngeal carriage at age 7 months. Efficacy against ear disease concurrent with carriage of vaccine-related serotypes (a more specific outcome) suggests 23vPPV in pregnancy may complement childhood pneumococcal vaccination programs.

When measuring a functional antibody response to pneumococcal immunization, it is imperative that a specific, reproducible, accurate, and standardized assay with acceptable inter- and intra-assay variation be advocated internationally to allow for meaningful comparison of results between laboratories. We report here the results of a collaboration between 3 international laboratories testing 30 pediatric samples against the 13 serotypes in Prevenar13. Opsonophagocytic assays are used to measure functional antibodies important in protection against pneumococcal capsular antigens. There have been efforts to standardize these methods, as the assays are commonly used to measure vaccine immunogenicity. We report here the results from three international laboratories using their own methods, based on the recommended WHO standard method. We tested 30 pediatric sera, before and after administration of a 13-valent conjugate pneumococcal vaccine, against all 13 serotypes. The three laboratories demonstrated good agreement using their own standardized multiplex opsonophagocytosis assay protocols, particularly postimmunization for those serotypes in the vaccine. While serotype-specific IgG methods have already been internationally standardized and are currently used as a measure of vaccine immunogenicity, this report demonstrates that despite minor differences in methods and a minor variation in response to nonvaccine serotypes, the results from opsonophagocytic assays across the three laboratories may be compared with confidence. IMPORTANCE When measuring a functional antibody response to pneumococcal immunization, it is imperative that a specific, reproducible, accurate, and standardized assay with acceptable inter- and intra-assay variation be advocated internationally to allow for meaningful comparison of results between laboratories. We report here the results of a collaboration between 3 international laboratories testing 30 pediatric samples against the 13 serotypes in Prevenar13.

Opsonophagocytic activity (OPA) was measured following reduced infant doses of 7-valent pneumococcal conjugate vaccine (PCV-7) with or without 23-valent pneumococcal polysaccharide vaccine (PPV-23) at 12 months, and subsequent re-exposure to a small dose of pneumococcal polysaccharide antigens (mPPS) at 17 months. Fijian infants were randomized to receive 0, 1, 2, or 3 PCV-7 doses. Half received PPV-23 at 12 months and all received mPPS at 17 months. OPA was performed on up to 14 serotypes. Three and 2 PCV-7 doses resulted in similar OPA for most PCV-7 serotypes up to 9 months and for half of the serotypes at 12 months. A single dose improved OPA compared with the unvaccinated group. PPV-23 significantly improved OPA for all serotypes tested but in general, was associated with diminished responses following re-challenge.

Quantitation of specific IgG to polysaccharides (serotypes) of Streptococcus pneumoniae provides the basis for evaluating vaccine efficacy. Different enzyme-linked immunosorbent assay (ELISA) methods are used internationally, making comparisons between laboratories difficult. We undertook an inter-laboratory comparison between two international laboratories performing serotype-specific IgG ELISAs using a panel of well-characterized serum samples: the Murdoch Childrens Research Institute Pneumococcal Laboratory (Melbourne, Australia) and the Vaccine Immunology Laboratory, National Public Health Institute (Helsinki, Finland). While good agreement was found for the inter-laboratory comparison for most serotypes, differences in ELISA methodology influenced specific IgG measurement. Therefore, use of the World Health Organization (WHO)-based ELISA methods for measurement of serotype-specific IgG is reliable, accurate and provides consistent results between international laboratories.

Fijian infants aged 6 weeks were stratified by ethnicity and randomized to receive 0, 1, 2, or 3 PCV-7 doses with or without the 23-valent pneumococcal polysaccharide vaccine (PPV-23) at 12 months. Strong booster effects for all 7 PCV-7 serotypes were elicited, and for 4/7 serotypes these responses were highest in the single PCV-7 group. There were fourfold rises in GMC for all non-PCV-7 serotypes. By 17 months the PPV-23 group still had significantly higher GMC (each p<0.001) for all serotypes. The PPV-23 was well tolerated and induced excellent responses for all serotypes which were greatest in the single PCV-7 group.

•Epidemiological data show BCG decreases infant mortality from diseases other than TB.•That BCG has non-specific immunological effects is well recognised.•We compared infants BCG-immunised at birth with non-BCG-immunised infants.•We measured antibody levels following pneumococcal, Hib, tetanus and hepatitis B immunisation.•BCG immunisation at birth influenced the subsequent antibody response to routine immunisations. Bacille Calmette-Guérin (BCG) is one of the most commonly administered vaccines worldwide. In addition to protection against tuberculosis (TB), evidence suggests that BCG immunisation has a number of additional beneficial non-specific immunological effects. These include a reduction in overall infant and child mortality attributable to causes other than TB in high-mortality regions. The antibody response to immunisations provides an opportunity to investigate the influence of BCG on the immune response to unrelated antigens. This study compared the antibody response to routine immunisations in BCG-immunised and non-BCG-immunised infants. BCG-immunised infants were recruited from a related study in which BCG was given at birth and non-BCG-immunised infants were recruited from immunisation clinics. All infants received their routine immunisations according to the Australian National Immunisation Program. Concentrations of antibodies against pneumococcal (anti-Pn Ps), Haemophilus influenzae type B (anti-Hib), tetanus toxoid (anti-TT) and hepatitis B surface (anti-HBs) antigen were measured four weeks after the last (six month) set of infant immunisations. A total of 127 parents agreed for their infants to take part in the study of which 108 were included in the final analysis (56 BCG-immunised and 52 non-BCG-immunised). The geometric mean concentration (GMC) of anti-Pn Ps IgG for all serotypes, anti-Hib IgG and anti-TT IgG were higher in the BCG-immunised group than the non-BCG-immunised group. This difference reached statistical significance for serotype 9V (p<0.01) and 18C (p=0.04). The GMC of anti-HBs IgG was lower in the BCG-immunised group than the non-BCG-immunised group (p=0.03). The majority of participants in both groups had antibody levels above the protective threshold. BCG immunisation at birth influences the antibody response to routine immunisations administered later in infancy. This has important implications for the introduction of both pneumococcal conjugate and novel TB vaccines in resource-limited countries.