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Updated: Jun 29, 2025
Experimental Human Pneumococcal Carriage
Published on: February 15, 2013
Pneumococcal conjugate vaccination schedules in infants-acquisition, immunogenicity, and pneumococcal conjugate and
Grant A Mackenzie1,2,3,4, Isaac Osei5,6, Rasheed Salaudeen5
1MRC Unit The Gambia at London School of Hygiene & Tropical Medicine, Fajara, The Gambia. gmackenzie@mrc.gm.
Insights
This study evaluates a reduced-dose pneumococcal conjugate vaccine (PCV) schedule to lower costs and improve global access. The research assesses immunogenicity and pneumococcal acquisition rates for a new PCV vaccination strategy.
Area of Science:
- Immunology
- Vaccinology
- Public Health
Background:
- Pneumococcal conjugate vaccine (PCV) effectiveness is proven, but high costs limit global access and sustainability in low-income countries.
- Reducing PCV program costs is crucial for wider vaccine introduction and long-term viability.
- A large-scale, population-level trial (PVS) is underway to assess an alternative, reduced-dose PCV schedule.
Purpose of the Study:
- This statistical analysis plan (SAP) details the PVS-AcqImm cohort, follow-up criteria, and analysis methods.
- The SAP defines primary endpoints and outlines how adherence to interventions will be reported.
- Accounting for clustering effects and avoiding bias through pre-defined analysis are key objectives.
Main Methods:
- A prospective, cluster-randomised trial (PVS-AcqImm) compares a reduced-dose PCV schedule (1 dose at 6 weeks, booster at 9 months) to the standard schedule (3 primary doses).
- The study investigates immunogenicity (anti-pneumococcal IgG) and pneumococcal acquisition rates.
- Yellow fever vaccine co-administration is also assessed in sub-groups.
Main Results:
- Primary endpoints include anti-pneumococcal IgG concentrations at 18 months, yellow fever antibody titres, and nasopharyngeal pneumococcal acquisition rates.
- Laboratory endpoints are masked, while participants and field staff are not masked to group allocation.
- The trial involves 28 clusters, with approximately equal numbers of participants in each arm, and specific numbers for acquisition and immunogenicity sub-studies.
Conclusions:
- The SAP provides a framework for unbiased analysis of the PVS-AcqImm trial data.
- This research aims to provide evidence for a cost-effective PCV schedule, potentially increasing global vaccine coverage.
- Findings will inform strategies for sustainable PCV programs in resource-limited settings.
Rationale:
The effectiveness of immunisation with pneumococcal conjugate vaccine (PCV) has been demonstrated in many countries. However, the global impact of PCV is limited by its cost, which has prevented its introduction in some countries. Reducing the cost of PCV programmes will facilitate further vaccine introductions and improve the sustainability of PCV in low-income countries when they transition from subsidised vaccine supply. We are conducting a large, population-level, cluster-randomised field trial (PVS) of an alternative reduced-dose schedule of PCV compared to the standard schedule. We are also conducting a nested sub-study at the individual level to investigate the immunogenicity of the two schedules and their effects on pneumococcal carriage acquisition (PVS-AcqImm).
Methods And Design:
PVS-AcqImm is a prospective, cluster-randomised trial of an alternative schedule of one dose of PCV scheduled at age 6 weeks with a booster dose at age 9 months compared to the standard of three primary doses scheduled at 6, 10, and 14 weeks of age. Sub-groups within the alternative schedule group receive yellow fever vaccine separately or co-administered with PCV at 9 months of age. The primary endpoints are (a) concentrations of vaccine-type anti-pneumococcal IgG at 18 months of age, (b) proportions with yellow fever neutralising antibody titre ≥ 1:8 4 weeks after separate or co-administration of PCV and yellow fever vaccines, and (c) rate of nasopharyngeal vaccine-type pneumococcal acquisition from 10-14 months of age. Participants and field staff are not masked to group allocation while measurement of the laboratory endpoints is masked. Approximately equal numbers of participants are resident in each of 28 randomly allocated geographic clusters (14 clusters in each group); 784 enrolled for acquisition measurements and 336 for immunogenicity measurements.
Purpose:
This statistical analysis plan (SAP) describes the PVS-AcqImm cohort and follow-up criteria to be used in different analyses. The SAP defines the endpoints and describes how adherence to the interventions will be presented. We describe the approach to analyses and how we will account for the effect of clustering. Defining the SAP prior to the conduct of analysis will avoid bias in analyses that may arise from prior knowledge of trial findings.
Trial Registration:
ISRCTN, ISRCTN7282161328. Registered on 28 November 2019. https://www.isrctn.com/ISRCTN72821613 .
Protocol:
MRCG SCC number 1670, LSHTM Ref 17683. Current protocol version: 6.0, 24 May 2021. Version: 1.0 (5 April 2023); SAP revisions-none.
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