Persistence of Immunogenicity Following Reduced PCV Dosing Schedules in South African Children

University of Witwatersrand, South Africa600 enrolled

Overview

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.

Study Type

OBSERVATIONAL

Enrollment

600

Conditions

Pneumonia Meningitis

Interventions

PCV10BIOLOGICAL

0.5 ml injection

PCV13BIOLOGICAL

0.5 ml injection

Eligibility

Sex: ALLMin age: 3 YearsMax age: 5 Years

Medical Language ↔ Plain English

Inclusion Criteria: 1. Children between and including the ages of 36 - 38 months of age at the time of first blood sampling; 2. Subjects who previously participated in the PCV1+1 study and received the full study vaccination regime as per protocol; 3. 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; 4. 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: 1. Receipt of any additional pneumococcal vaccine since the end of participation in the PCV1+1 study; 2. Any known or suspected immunodeficiency condition which could affect immune response to vaccination, including living with HIV; 3. Receipt of any immunoglobulins and/or blood products less than 6 months prior to blood sampling; 4. Parent/legal guardian unable or unwilling to attend scheduled study visits.

Locations (1)

Chris Hani Baragwanath Academic Hospital - DST/NRF VPD RMPRU

Soweto, Gauteng, South Africa

Outcomes

Primary Outcomes

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).

Time frame: 3, 4 and 5 years of age

Secondary Outcomes

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

Time frame: 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).

Time frame: 3, 4 and 5 years of age

Colonization outcome

To compare the prevalence of vaccine-serotype (stratified by PCV10 and PCV13 serotypes)

Time frame: 3, 4 and 5 years of age

Data from ClinicalTrials.gov

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