Immunogenicity after one, two or three doses and impact on the antibody response to coadministered antigens of a nonavalent pneumococcal conjugate vaccine in infants of Soweto, South Africa.
ABSTRACT Children <6 months of age are at increased risk of pneumococcal disease. The early immunogenicity of conjugate vaccines therefore may be important to prevent disease in young children.
To determine the immunogenicity of a nonavalent pneumococcal conjugate vaccine after one dose, two doses and three doses and its impact on the antibody response to coadministered antigens.
A total of 500 infants from Soweto were immunized at 6, 10 and 14 weeks of age with either placebo (n = 250) or 9-valent pneumococcal conjugate vaccine (n = 250) containing serotypes 1, 4, 5, 6B, 9V, 14, 18C, 19F and 23F conjugated to CRM(197) mutant diphtheria protein. Blood was taken for determination of serotype-specific IgG before the first dose and 1 month after each dose.
Before the first dose at 6 weeks of age >80% of infants had >0.15 microg/ml antibody to six of the nine antigens, >70% to serotypes 18C and 23F and >50% to serotype 4. Geometric mean concentrations (GMCs) after one dose ranged from 0.27 microg/ml for serotype 23F to 2.98 microg/ml for serotype 1; >90% of infants had serotype-specific antibody >0.15 microg/ml except for serotypes 23F (70%) and 6B (80%). After two doses GMCs ranged from 1.14 microg/ml for serotype 23F to 5.68 microg/ml for serotype 1; >95% of infants had serotype-specific antibody >0.15 microg/ml and >75% had >0.5 microg/ml for all nine serotypes. GMCs after three doses ranged from 2.73 microg/ml for serotype 23F to 6.18 microg/ml for serotype 5; >98% of infants had serotype-specific antibody >0.15 microg/ml and >92% had >0.5 microg/ml for all nine serotypes. Antibody concentrations after three doses were significantly higher to Haemophilus influenzae type b-polyribosylribitol phosphate vaccine in children who received pneumococcal conjugate vaccine, but they had lower antibodies to pertussis toxin than controls.
A single dose of this pneumococcal conjugate vaccine produces a potentially protective antibody response to most serotypes in the majority of children in this population.
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ABSTRACT: Despite the breadth of studies demonstrating benefits of pneumococcal conjugate vaccine (PCV), uncertainty remains regarding the optimal PCV dosing schedule in infants. We conducted a systematic literature review of PCV immunogenicity published from 1994 to 2010 (supplemented post hoc with studies from 2011). Studies included for analysis evaluated ≥2 doses of 7-valent or higher product (excluding Aventis-Pasteur PCV11) administered to nonhigh-risk infants ≤6 months of age. Impact of PCV schedule on geometric mean antibody concentration (GMC) and proportion of subjects over 0.35 mcg/mL were assessed at various time points; the GMC 1 month postdose 3 (for various dosing regimens) for serotypes 1, 5, 6B, 14, 19F and 23F was assessed in detail using random effects linear regression, adjusted for product, acellular diphtheria-tetanus-pertussis/whole-cell diphtheria- tetanus-pertussis coadministration, laboratory method, age at first dose and geographic region. From 61 studies, we evaluated 13 two-dose (2+0) and 65 three-dose primary schedules (3+0) without a booster dose, 11 "2+1" (2 primary plus booster) and 42 "3+1" schedules. The GMC after the primary series was higher following 3-dose schedules compared with 2-dose schedules for all serotypes except for serotype 1. Pre- and postbooster GMCs were generally similar regardless of whether 2 or 3 primary doses were given. GMCs were significantly higher for all serotypes when dose 3 was administered in the second year (2+1) compared with ≤6 months of age (3+0). While giving the third dose in the second year of life produces a higher antibody response than when given as part of the primary series in the first 6 months, the lower GMC between the 2-dose primary series and booster may result in less disease protection for infants in that interval than those who completed the 3-dose primary series. Theoretical advantages of higher antibodies induced by giving the third dose in the second year of life, such as increased protection against serotype 1 disease, longer duration of protection or more rapid induction of herd effects, need to be evaluated in practice.The Pediatric Infectious Disease Journal 01/2014; 33 Suppl 2(Suppl 2 Optimum Dosing of Pneumococcal Conjugate Vaccine For Infants 0 A Landscape Analysis of Evidence Supportin g Different Schedules):S119-29. DOI:10.1097/INF.0000000000000079 · 3.14 Impact FactorThis article is viewable in ResearchGate's enriched formatRG Format enables you to read in context with side-by-side figures, citations, and feedback from experts in your field.
SourceAvailable from: repository.unimelb.edu.au
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ABSTRACT: BACKGROUND AND OBJECTIVES: Variation in patient care or outcomes may indicate an opportunity to improve quality of care. We evaluated the variation in testing, treatment, hospitalization rates, and outcomes of febrile young infants in US pediatric emergency departments (EDs). METHODS: Retrospective cohort study of infants,90 days of age with a diagnosis code of fever who were evaluated in 1 of 37 pediatric EDs between July 1, 2011 and June 30, 2013. We assessed patient-and hospital-level variation in testing, treatment, and disposition for patients in 3 distinct age groups: <= 28, 29 to 56, and 57 to 89 days. We also compared interhospital variation for 3-day revisits and revisits resulting in hospitalization. RESULTS: We identified 35 070 ED visits that met inclusion criteria. The proportion of patients who underwent comprehensive evaluation, defined as urine, serum, and cerebrospinal fluid testing, decreased with increasing patient age: 72.0% (95% confidence interval [CI], 71.0-73.0) of neonates <= 28 days, 49.0% (95% CI, 48.2-49.8) of infants 29 to 56 days, and 13.1% (95% CI, 12.5-13.6) of infants 57 to 89 days. Significant interhospital variation was demonstrated in testing, treatment, and hospitalization rates overall and across all 3 age groups, with little interhospital variation in outcomes. Hospitalization rate in the overall cohort did not correlate with 3-day revisits (R-2 = 0.10, P = .06) or revisits resulting in hospitalization (R-2 = 0.08, P = .09). CONCLUSIONS: Substantial patient-and hospital-level variation was observed in the ED management of the febrile young infant, without concomitant differences in outcomes. Strategies to understand and address the modifiable sources of variation are needed.2014 American Academy of Pediatrics National Conference and Exhibition; 10/2014