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1.  Serotype-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 
Vaccine  2011;29(27):4499-4506.
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 booster 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.
doi:10.1016/j.vaccine.2011.04.038
PMCID: PMC3114163  PMID: 21539882
2.  Opsonophagocytic Activity Following a Reduced Dose 7-valent Pneumococcal Conjugate Vaccine Infant Primary Series and 23-valent Pneumococcal Polysaccharide Vaccine at 12 Months of Age 
Vaccine  2010;29(3):535-544.
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.
doi:10.1016/j.vaccine.2010.10.046
PMCID: PMC3011050  PMID: 21044669
pneumococcal vaccination; opsonophagocytic activity
3.  Pneumococcal Nasopharyngeal Carriage following Reduced Doses of a 7-Valent Pneumococcal Conjugate Vaccine and a 23-Valent Pneumococcal Polysaccharide Vaccine Booster▿ †  
Clinical and Vaccine Immunology : CVI  2010;17(12):1970-1976.
This study was conducted to evaluate the effect of a reduced-dose 7-valent pneumococcal conjugate vaccine (PCV) primary series followed by a 23-valent pneumococcal polysaccharide vaccine (23vPPS) booster on nasopharyngeal (NP) pneumococcal carriage. For this purpose, Fijian infants aged 6 weeks were randomized to receive 0, 1, 2, or 3 PCV doses. Within each group, half received 23vPPS at 12 months. NP swabs were taken at 6, 9, 12, and 17 months and were cultured for Streptococcus pneumoniae. Isolates were serotyped by multiplex PCR and a reverse line blot assay. There were no significant differences in PCV vaccine type (VT) carriage between the 3- and 2-dose groups at 12 months. NP VT carriage was significantly higher (P, <0.01) in the unvaccinated group than in the 3-dose group at the age of 9 months. There appeared to be a PCV dose effect in the cumulative proportion of infants carrying the VT, with less VT carriage occurring with more doses of PCV. Non-PCV serotype (NVT) carriage rates were similar for all PCV groups. When groups were pooled by receipt or nonreceipt of 23vPPS at 12 months, there were no differences in pneumococcal, VT, or NVT carriage rates between the 2 groups at the age of 17 months. In conclusion, there appeared to be a PCV dose effect on VT carriage, with less VT carriage occurring with more doses of PCV. By the age of 17 months, NVT carriage rates were similar for all groups. 23vPPS had no impact on carriage, despite the substantial boosts in antibody levels.
doi:10.1128/CVI.00117-10
PMCID: PMC3008188  PMID: 20943882
4.  Hyporesponsiveness to Re-challenge Dose Following Pneumococcal Polysaccharide Vaccine at 12 Months of Age, a Randomized Controlled Trial 
Vaccine  2010;28(19):3341-3349.
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.
doi:10.1016/j.vaccine.2010.02.087
PMCID: PMC2854305  PMID: 20206670
5.  Safety and Immunogenicity of the 23-Valent Pneumococcal Polysaccharide Vaccine at 12 months of age, following One, Two, or Threes Doses of the 7-valent Pneumococcal Conjugate Vaccine in Infancy 
Vaccine  2010;28(18):3086-3094.
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.
doi:10.1016/j.vaccine.2010.02.065
PMCID: PMC2857918  PMID: 20199764
Pneumococcal; polysaccharide; booster
6.  Immunogenicity Following One, Two, or Three Doses of the 7-valent Pneumococcal Conjugate Vaccine 
Vaccine  2009;27(41):5685-5691.
The aim was to identify an appropriate infant pneumococcal vaccination strategy for resource poor countries. Fijian infants received 0, 1, 2, or 3 doses of 7-valent pneumococcal conjugate vaccine (PCV) in early infancy. Following 3 PCV doses, geometric mean concentration (GMC) to all 7 serotypes were ≥ 1.0μg/mL, and >85% of children achieved antibody levels ≥0.35μg/mL at 18 weeks. Following 2 doses, GMC were lower for 6B, 14, and 23F, but higher for 19F compared with 3 doses. Following a single dose, significant responses were seen for all serotypes post primary series compared with the unvaccinated. By 12 months, differences between 2 and 3 doses persisted for serotype 14 only. Although GMC following 3 doses are higher than after 2 doses, the differences were small. A single dose may offer some protection for most serotypes.
doi:10.1016/j.vaccine.2009.06.098
PMCID: PMC2734870  PMID: 19616498
Pneumococcal conjugate vaccine

Results 1-6 (6)