Immunogenicity and safety of a 10-valent pneumococcal conjugate vaccine administered as a 2 + 1 schedule to healthy infants in The Gambia: a single-centre, double-blind, active-controlled, randomised, phase 3 trial.

BACKGROUND: Three pneumococcal conjugate vaccines (PCVs) are currently licensed and WHO prequalified for supply by UN agencies. Here, we aimed to investigate the safety and immunogenicity of SIIPL-PCV compared with PHiD-CV and PCV13, when administered to infants according to a 2 + 1 schedule. METHODS: This single-centre, double-blind, active-controlled, randomised, phase 3 trial was done in Medical Research Council Unit The Gambia at the London School of Hygiene & Tropical Medicine clinical trial facilities within two government health centres in the western region of The Gambia. Healthy, PCV-naive infants aged 6-8 weeks were enrolled if they weighed at least 3·5 kg and had no clinically significant health complaints, as determined by history and clinical examination. Eligible infants were randomly assigned (1:1:1) to receive either SIIPL-PCV, PHiD-CV, or PCV13 using permuted blocks of variable size. Parents and the trial staff assessing all study outcomes were masked to vaccine group. The first PCV vaccine was given with other routine Expanded Programme on Immunization vaccines when infants were aged 6-8 weeks (visit 1). At visit 2, routine vaccines alone (without a PCV) were administered. At visit 3, the second dose of the PCV was administered alongside other routine vaccines. At visit 4, a blood sample was collected. Visits 1-4 took place at intervals of 4 weeks. The booster PCV was administered at age 9-18 months (visit 5), with final follow-up 4 weeks after the booster (visit 6). The primary immunogenicity outcome compared the serotype-specific IgG geometric mean concentrations (GMCs) generated by SIIPL-PCV with those generated by PHiD-CV and PCV13, 4 weeks after the booster. We used descriptive 95% CIs without adjustment for multiplicity. Immunogenicity analyses were done in the per protocol population (defined as all children who received all the assigned study vaccines, who had an immunogenicity measurement available, and who had no protocol deviations that might interfere with the immunogenicity assessment). This trial was registered with the Pan African Clinical Trials Registry, PACTR201907754270299, and ClinicalTrials.gov, NCT03896477. FINDINGS: Between July 18 and Nov 14, 2019, 745 infants were assessed for study eligibility. Of these, 85 infants (11%) were ineligible and 660 (89%) were enrolled and randomly assigned to receive SIIPL-PCV (n=220), PHiD-CV (n=220), or PCV13 (n=220). 602 infants (91%) were included in the per protocol immunogenicity population. The median age at vaccination was 46 days (range 42-56). 342 infants (52%) were female and 318 (48%) were male. Post-booster serotype-specific IgG GMCs generated by SIIPL-PCV ranged from 1·54 µg/mL (95% CI 1·38-1·73) for serotype 5 to 12·46 µg/mL (11·07-14·01) for serotype 6B. Post-booster GMCs against shared serotypes generated by PHiD-CV ranged from 0·80 µg/mL (0·72-0·88) for serotype 5 to 17·31 µg/mL (14·83-20·20) for serotype 19F. Post-booster GMCs generated by PCV13 ranged from 2·04 µg/mL (1·86-2·24) for serotype 5 to 15·54 µg/mL (13·71-17·60) for serotype 6B. Post-booster IgG GMCs generated by SIIPL-PCV were higher than those generated by PHiD-CV for seven of the eight shared serotypes (1, 5, 6B, 7F, 9V, 14, and 23F). The GMC generated by serotype 19F was higher after PHiD-CV. The SIIPL-PCV to PHiD-CV GMC ratios for shared serotypes ranged from 0·64 (95% CI 0·52-0·79) for serotype 19F to 2·91 (2·47-3·44) for serotype 1. The serotype 1 GMC generated by SIIPL-PCV was higher than that generated by PCV13, whereas serotype 5, 6A, 19A, and 19F GMCs were higher after PCV13. The SIIPL-PCV to PCV13 GMC ratios ranged from 0·72 (0·60-0·87) for serotype 19A to 1·44 (1·23-1·69) for serotype 1. INTERPRETATION: SIIPL-PCV was safe and immunogenic when given to infants in The Gambia according to a 2 + 1 schedule. This PCV is expected to provide similar protection against invasive and mucosal pneumococcal disease to the protection provided by PCV13 and PHiD-CV, for which effectiveness data are available. Generating post-implementation data on the impact of SIIPL-PCV on pneumococcal disease endpoints remains important. FUNDING: Bill & Melinda Gates Foundation.

COVID-19-related research in Africa: a cross-sectional review of the International Clinical Trial Registration Platform (ICTRP).

OBJECTIVE: The declaration of the coronavirus disease (COVID-19), a pandemic in early 2020, has seen an upsurge in research globally to fill gaps in the epidemiology of the SARS-CoV-2 virus impact on health care and clinical management, as well as possible prevention and treatment modalities. Published literature on the different types of COVID-19 research conducted globally is varied and is particularly limited in Africa. This study sets out to describe the COVID-19-related research registered and conducted on the African continent. METHODS: This is a cross-sectional study of all COVID-19-related studies available in the WHO's International Clinical Trials Registry Platform (ICTRP) repository. We extracted studies registered from March 1, 2020, to July 15, 2021. A descriptive analysis of the extracted data was performed, and the findings were presented. RESULTS: At extraction, a total of 12,533 COVID-19-related studies were listed on the ICTRP portal. We included 9803 studies, after excluding 2060 duplicate records and 686 records without a site/country. While 9347 studies (96%) were conducted outside of Africa, only 456 studies (4%) were conducted in the African continent, of which 270 (59.2%) were interventional studies, and 184 (40.4%) were observational studies. About 80% of the studies were conducted in Egypt and South Africa, and most of these involved testing of drugs and biologicals. CONCLUSION: The African continent hosts considerably fewer COVID-19-related research compared to other parts of the world. This may have implications on scientific evidence available for implementing COVID-19 control efforts. There is, therefore, a need for local funding and ownership of research projects and north-south collaboration in research.

Considerations for Establishing Successful Coronavirus Disease Vaccination Programs in Africa.

The accelerated development of coronavirus disease (COVID-19) candidate vaccines is intended to achieve worldwide immunity. Ensuring COVID-19 vaccination is crucial to stemming the pandemic, reclaiming everyday life, and helping restore economies. However, challenges exist to deploying these vaccines, especially in resource-limited sub-Saharan Africa. In this article, we highlight lessons learned from previous efforts to scale up vaccine distribution and offer considerations for policymakers and key stakeholders to use for successful COVID-19 vaccination rollout in Africa. These considerations range from improving weak infrastructure for managing data and identifying adverse events after immunization to considering financing options for overcoming the logistical challenges of vaccination campaigns and generating demand for vaccine uptake. In addition, providing COVID-19 vaccination can be used to promote the adoption of universal healthcare, especially in sub-Saharan Africa countries.

Acute respiratory distress syndrome (ARDS) as an adverse event following immunization: Case definition & guidelines for data collection, analysis, and presentation of immunization safety data.

This is a Brighton Collaboration Case Definition of the term "Acute Respiratory Distress Syndrome - ARDS" to be utilized in the evaluation of adverse events following immunization. The Case Definition was developed by a group of experts convened by the Coalition for Epidemic Preparedness Innovations (CEPI) in the context of active development of vaccines for SARS-CoV-2 vaccines and other emerging pathogens. The case definition format of the Brighton Collaboration was followed to develop a consensus definition and defined levels of certainty, after an exhaustive review of the literature and expert consultation. The document underwent peer review by the Brighton Collaboration Network and by selected Expert Reviewers prior to submission. The comments of the reviewers were taken into consideration and edits incorporated in this final manuscript.