Paediatrics (RCH) - Research Publications
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ItemNo Preview AvailableImpaired serotype-specific immune function following pneumococcal vaccination in infants with prior carriage(ELSEVIER SCI LTD, 2014-04-25)The impact of prior nasopharyngeal carriage on serotype-specific IgG responses following immunization with pneumococcal conjugate vaccines (PCV) has recently been described. This report extends these findings to describe the attenuation of functional immune responses following 23-valent pneumococcal polysaccharide vaccination (PPS). We report the attenuation of immune responses following booster with the 23-valent pneumococcal polysaccharide vaccination (PPS) in infants with prior nasopharyngeal carriage of Streptococcus pneumoniae. Fijian infants who were part of a phase II randomized, controlled trial of reduced dose PCV7 schedules were the basis of this study. Pneumococcal carriage was determined at 6, 9 and 12 months of age, prior to PPS immunization. Serum samples collected at 18 weeks (post-PCV7), 12 months (pre-PPS), 12.5 months and 17 months (post-PPS) of age were assessed for serotype-specific IgG and opsonophagocytic responses. The most frequently carried serotypes were 6B (N=11), 19F (N=14) and 23F (N=23). Significantly lower serotype-specific IgG for 19F, 23F but not 6B post-PPS were detected in infants with homologous serotype carriage prior to PPS compared with non-carriers (N=230). However, OPA levels for 6B and 23F were lower in infants that carried these serotypes. Pneumococcal carriage with 19F or 23F at any time prior to PPS immunization in infants at 12 months of age who were previously primed with PCV resulted in serotype-specific hyporesponsiveness that persisted until 17 months of age. These results may have implications for the timing of infant vaccine schedules, particularly in high disease burden settings.
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ItemSafety and immunogenicity of the 23-valent pneumococcal polysaccharide vaccine at 12 months of age, following one, two, or three doses of the 7-valent pneumococcal conjugate vaccine in infancy(ELSEVIER SCI LTD, 2010-04-19)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.
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ItemHyporesponsiveness to re-challenge dose following pneumococcal polysaccharide vaccine at 12 months of age, a randomized controlled trial(ELSEVIER SCI LTD, 2010-04-26)BACKGROUND: 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). METHODS: 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. FINDINGS: 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). INTERPRETATION: 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.
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ItemAntibodies to serotype 9V exhibit novel serogroup cross-reactivity following infant pneumococcal immunization(ELSEVIER SCI LTD, 2010-05-14)Cross-reactivity within the pneumococcal immune response was examined in this study. Significant cross-reactivity between serotypes 9V, 15B and 19A was identified in infant post-immunization serum that could not be effectively titrated during specific IgG measurements. Pre-absorption using serotype 9V inhibited this cross-reactivity and normalized titratability in the WHO ELISA for serotypes 15B and 19A. However, this did not affect functional avid IgG and was associated with fewer pneumococcal conjugate vaccine (PCV) doses, suggesting that cross-reactive antibodies were of low avidity. The results in this study have important implications for assessment of vaccine immunogenicity.
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ItemInfants aged 12 months can mount adequate serotype-specific IgG responses to pneumococcal polysaccharide vaccine(MOSBY-ELSEVIER, 2010-08)This is the first study examining serotype-specific IgG responses following immunization with the polysaccharide vaccine Pneumovax® in infants aged 12 months in the absence of prior pneumococcal conjugate vaccine priming.
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ItemSerotype-specific avidity is achieved following a single dose of the 7-valent pneumococcal conjugate vaccine, and is enhanced by 23-valent pneumococcal polysaccharide booster at 12 months(ELSEVIER SCI LTD, 2011-06-15)AIM: To evaluate whether the avidity of serotype-specific IgG to pneumococcal serotypes is enhanced by an increased number of doses of the 7-valent pneumococcal conjugate vaccine (PCV) in infancy or by a 12 month 23-valent pneumococcal polysaccharide vaccine (23vPPS) booster, and/or subsequent re-exposure to a small dose of pneumococcal polysaccharide antigens (mPPS) at 17 months. METHODS: Fijian infants aged 6 weeks were recruited, stratified by ethnicity and randomized to 8 groups to receive 0, 1, 2, or 3 doses of PCV, with or without 23vPPS at 12 months. All children received mPPS at 17 months of age. Avidity of serotype-specific IgG for PCV serotypes in the first 12 months and for all 23vPPS serotypes thereafter was assessed by EIA after sodium thiocyanate elution. RESULTS: At one month post primary series, the 2 and 3 PCV dose groups demonstrated similar avidity, with the single dose group tending to have lower avidity. However, by age 9 months, the single dose group had similar avidity to the 2 and 3 PCV groups for most serotypes. The 23vPPS booster enhanced affinity maturation for most serotypes and this was most marked in those groups that received a single PCV dose. There was little further increase following the mPPS. CONCLUSIONS: By 9 months of age, similar avidity can be induced following one, 2 or 3 doses of PCV. A 23vPPS booster at 12 months enhanced affinity maturation with an increase in antibody avidity for most serotypes. Subsequent re-challenge with mPPS at 17 months did not further enhance the avidity of serotype-specific response in the 12 month 23vPPS groups.
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ItemOpsonophagocytic activity following a reduced dose 7-valent pneumococcal conjugate vaccine infant primary series and 23-valent pneumococcal polysaccharide vaccine at 12 months of age(ELSEVIER SCI LTD, 2011-01-10)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.
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ItemAge-and serotype-dependent antibody response to pneumococcal polysaccharides Reply(MOSBY-ELSEVIER, 2011-04)
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ItemPneumococcal polysaccharide vaccine at 12 months of age produces functional immune responses(MOSBY-ELSEVIER, 2012-03)BACKGROUND: Infections with Streptococcus pneumoniae (pneumococcus) are a cause of significant child mortality. Pneumococcal glycoconjugate vaccines are expensive and provide limited serotype coverage. The 23-valent pneumococcal polysaccharide vaccine (Pneumovax) might provide wider serotype coverage but is reported to be weakly immunogenic in children less than 2 years of age. We have previously reported that Pneumovax administered to healthy 12-month-old Fijian infants elicits significant serotype-specific IgG responses. However, the functional capacity of these responses in 12-month-old infants is not known. OBJECTIVE: We sought to assess the functional, serotype-specific immune response of 12-month-old infants after immunization with Pneumovax. METHODS: Functional responses of 12-month-old infants were assessed by using the opsonophagocytic and antibody avidity assay against 8 serotypes and 23 serotypes, respectively. RESULTS: Seventy-one percent of infants produced strong opsonophagocytic activity against 4 of 8 serotypes, and 30% produced high-avidity serotype-specific IgG antibodies to 10 of 23 serotypes at 2 weeks after Pneumovax. Responses were protective for most serotypes that cause disease in Western countries, whereas responses to most of the epidemiologically relevant serotypes for developing countries were low. CONCLUSION: This is the first comprehensive study evaluating the functional antibody response to Pneumovax in 12-month-old infants. Pneumovax induced functional antibody responses to several serotypes causing disease in Western countries but induced poorer responses to serotypes that are responsible for the majority of disease in developing countries. Pneumovax might be of benefit in some populations, but further studies are required before this can be recommended in developing countries.