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This study will evaluate the persistence of immunogenicity following a reduced dosing schedule of 10- or 13-valent Pneumococcal Conjugate Vaccine (PCV10, PCV13). This is the follow-up of a randomized controlled trial in which children received a single priming dose of PCV10 or PCV13 (at 6 or 14 weeks of age) followed by booster dose at 9 months of age (1+1 schedule), compared to a 2+1 PCV schedule (6, 14 weeks of age and 9 months of age).
Between 2017 and 2019, we conducted an open-labelled, randomized controlled trial to evaluate for non-inferiority in the post-booster serotype-specific geometric mean concentrations (GMC's) in children randomized to receive either PCV10 or PCV13 as a 1+1 schedule (with the first dose occurring either at 6 or 14 weeks of age) compared to infants who received a two dose primary series (6 and 14 weeks of age). All six study groups received a booster dose at 40 weeks of age, and serotype-specific IgG and opsonophagocytic activity was measured one-month post booster. Subjects were planned to be followed-up until 18 months of age as part of the initial study. In the present study, we propose to extent the follow-up of the cohort to include annual visit at 3, 4 and 5 years of age, to evaluate the sustainability of the humoral immune response of the different PCV dosing schedules.
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| PCV10 1+1, 6 weeks & 9 months | Follow-up of children who were previously randomized to PCV10 (Synflorix 0.5ml injection) administered at 6 weeks and 9 months of age. |
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| PCV13 1+1, 6 weeks & 9 months | Follow-up of children who were previously randomized to PCV13 (Prevnar 13, 0.5ml injection) administered at 6 weeks and 9 months of age. |
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| PCV10 1+1, 14 weeks & 9 months | Follow-up of children who were previously randomized to PCV10 (Synflorix 0.5ml injection) administered at 14 weeks and 9 months of age. |
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| PCV13 1+1, 14 weeks & 9 months | Follow-up of children who were previously randomized to PCV13 (Prevnar 13, 0.5ml injection) administered at 14 weeks and 9 months of age. |
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| PCV10 2+1, 6&14 weeks & 9 months | Follow-up of children who were previously randomized to PCV10 (Synflorix 0.5ml injection) administered at 6 weeks, 14 weeks and 9 months of age. |
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| PCV13 2+1, 6&14 weeks & 9 months |
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| PCV10 | Biological | 0.5 ml injection |
|
| Measure | Description | Time Frame |
|---|---|---|
| Serotype specific geometric mean antibody concentrations (GMC) | To evaluate persistence of vaccine-serotype specific GMCs at 3, 4 and 5 years of age between children receiving differing 1+1 dosing schedules compared to the 2+1 dosing schedule of the same vaccine formulation (i.e. PCV10 or PCV13). | 3, 4 and 5 years of age |
| Measure | Description | Time Frame |
|---|---|---|
| Modified threshold of protection | To evaluate persistence of vaccine-serotype specific serum IgG antibody concentration above the WHO-defined putative threshold for protection (≥0.35 µg/mL) and the modified serotype-specific correlate of protection against IPD as proposed by Andrews et al.(17) at 3, 4 and 5 years of between children with differing 1+1 dosing schedules compared to the 2+1 dosing schedule of the same vaccine formulation |
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Inclusion Criteria:
Exclusion Criteria:
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All participants who completed the PCV1+1 study and received all vaccines as specified per study protocol will be contacted to participate.
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| Name | Affiliation | Role |
|---|---|---|
| Shabir A Madhi, MD PhD | University of Witwatersrand, South Africa | Principal Investigator |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| Chris Hani Baragwanath Academic Hospital - DST/NRF VPD RMPRU | Soweto | Gauteng | 2013 | South Africa |
| PubMed Identifier | Type | Citation | Retractions |
|---|---|---|---|
| 39417218 | Derived | Olwagen CP, Izu A, Van der Merwe L, Jose L, Koen A, Madhi SA. Single priming and a booster dose of 10-valent and 13-valent pneumococcal conjugate vaccine (PCV) maintains suppression of vaccine serotype colonization in South African children at 3, 4, and 5 years of age: a single-centre, open-labelled, randomized trial. Expert Rev Vaccines. 2024 Jan-Dec;23(1):1011-1019. doi: 10.1080/14760584.2024.2417856. Epub 2024 Oct 22. |
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| ID | Term |
|---|---|
| D011014 | Pneumonia |
| D008581 | Meningitis |
| ID | Term |
|---|---|
| D012141 | Respiratory Tract Infections |
| D007239 | Infections |
| D008171 | Lung Diseases |
| D012140 | Respiratory Tract Diseases |
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| ID | Term |
|---|---|
| C586648 | 10-valent pneumococcal conjugate vaccine |
| C547294 | PHiD-CV vaccine |
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Serum and nasopharyngeal swabs
Follow-up of children who were previously randomized to PCV13 (Prevnar 13, 0.5ml injection) administered at 6 weeks, 14 weeks and 9 months of age. |
|
| PCV13 | Biological | 0.5 ml injection |
|
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| 3, 4 and 5 years of age |
| Comparison between 6-week and 14-week primary dose | To evaluate persistence of vaccine-serotype specific serum IgG antibody concentration above the WHO-defined putative threshold for protection (≥0.35 µg/mL), the modified serotype-specific correlate of protection against IPD as proposed by Andrews et al. (17) and GMC's at 3, 4 and 5 years in children receiving the 1+1 dosing schedule at either 6 weeks of age compared to those who received it at 14 weeks of age, stratified for the individual vaccine formulation (PCV10 and PCV13). | 3, 4 and 5 years of age |
| Colonization outcome | To compare the prevalence of vaccine-serotype (stratified by PCV10 and PCV13 serotypes) | 3, 4 and 5 years of age |
| D000090862 |
| Neuroinflammatory Diseases |
| D009422 | Nervous System Diseases |