PCV1+1_FU: Persistence of Immunogenicity Following Reduced PCV Dosing Schedules in South African Children
Study Details
Study Description
Brief Summary
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).
| Condition or Disease | Intervention/Treatment | Phase |
|---|---|---|
|
Detailed Description
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.
Study Design
Arms and Interventions
| Arm | Intervention/Treatment |
|---|---|
| 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. |
Biological: PCV10
0.5 ml injection
Other Names:
|
| 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. |
Biological: PCV13
0.5 ml injection
Other Names:
|
| 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. |
Biological: PCV10
0.5 ml injection
Other Names:
|
| 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. |
Biological: PCV13
0.5 ml injection
Other Names:
|
| 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. |
Biological: PCV10
0.5 ml injection
Other Names:
|
| PCV13 2+1, 6&14 weeks & 9 months 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. |
Biological: PCV13
0.5 ml injection
Other Names:
|
Outcome Measures
Primary Outcome Measures
- Serotype specific geometric mean antibody concentrations (GMC) [3, 4 and 5 years of age]
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).
Secondary Outcome Measures
- Modified threshold of protection [3, 4 and 5 years of age]
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
- Comparison between 6-week and 14-week primary dose [3, 4 and 5 years of age]
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).
Other Outcome Measures
- Colonization outcome [3, 4 and 5 years of age]
To compare the prevalence of vaccine-serotype (stratified by PCV10 and PCV13 serotypes) and non-vaccine serotype nasopharyngeal colonization at 3, 4 and 5 years of age for the 1+1 dosing schedule groups compared to the 2+1 groups.
Eligibility Criteria
Criteria
Inclusion Criteria:
-
Children between and including the ages of 36 - 38 months of age at the time of first blood sampling;
-
Subjects who previously participated in the PCV1+1 study and received the full study vaccination regime as per protocol;
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The parent or legal guardian of the child must be able and willing to provide written informed consent for all 3 visits and comply with all study requirements;
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The parent or legal guardian of the child must indicate the intention to remain in the study area for the duration of the trial - or be willing to bring the child for all visits.
Exclusion Criteria:
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Receipt of any additional pneumococcal vaccine since the end of participation in the PCV1+1 study;
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Any known or suspected immunodeficiency condition which could affect immune response to vaccination, including living with HIV;
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Receipt of any immunoglobulins and/or blood products less than 6 months prior to blood sampling;
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Parent/legal guardian unable or unwilling to attend scheduled study visits.
Contacts and Locations
Locations
| Site | City | State | Country | Postal Code | |
|---|---|---|---|---|---|
| 1 | Chris Hani Baragwanath Academic Hospital - DST/NRF VPD RMPRU | Soweto | Gauteng | South Africa | 2013 |
Sponsors and Collaborators
- University of Witwatersrand, South Africa
Investigators
- Principal Investigator: Shabir A Madhi, MD PhD, University of the Witwatersrand, South Africa
Study Documents (Full-Text)
None provided.More Information
Publications
None provided.- PCV1+1 follow-up