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. 2024 Dec 24:9:733.
doi: 10.12688/wellcomeopenres.23138.1. eCollection 2024.

Booster Vaccination against Yellow Fever in Gambian children-(BoVY) -a Phase 3 clinical trial to establish safety and immunogenicity of repeated YF vaccination in healthy Gambian children of different ages

Beate Kampmann  1   2   3 , Caitlin Pley  1 , Julia Strandmark  2 , Mam Nabou Leigh  2 , Peter Ndow  2 , Ed Clarke  2   3 , Elishia Roberts  2 , Amadou Faal  2 , David Jeffries  2   3 , Ebrima Kanteh  2
Affiliations

Booster Vaccination against Yellow Fever in Gambian children-(BoVY) -a Phase 3 clinical trial to establish safety and immunogenicity of repeated YF vaccination in healthy Gambian children of different ages

Beate Kampmann et al. Wellcome Open Res. .

Abstract

Background: Yellow fever (YF) is a mosquito-borne and recently re-emerging viral haemorrhagic fever endemic to sub-Saharan Africa and South America. A highly effective vaccine against YF is licensed and recommended as part of routine childhood immunisation as a single dose at 9 months. Recent observational data demonstrate waning immunity following single primary vaccination and suggest that children in endemic areas may require booster vaccination.

Methods: This open-label, non-randomised clinical vaccine trial (ClinicalTrials.gov, NCT05332197, registered on 31 March 2022, URL: https://clinicaltrials.gov/study/NCT05332197) will assess the safety and immunogenicity of a booster dose of the licensed 17D YF vaccine in Gambian children. The trial will recruit 750 children in three cohorts of different ages (250 each). All children were vaccinated with the 17D YF vaccine at 9-10 months of age as part of clinical trials run by the Medical Research Council (MRC) Unit The Gambia, and are thus well-characterised, including basic clinical, anthropometric, and post-primary immunogenicity data. The children will receive booster doses at 15 months, 4 years, or 8.5 years. Serum samples will be taken before and 28 days after the booster, with additional sampling for exploratory endpoints in subgroups. Adverse events are solicited for the first three days following vaccination and recorded throughout the study period. The primary objective of the trial is to describe the safety and immunogenicity of the booster in the different age cohorts. Secondary objectives are to characterise the rate of sero-reversion (change from seropositive to seronegative) over a period of 9 months to 8 years following single primary vaccination and to profile the immune response to the booster to explore underlying mechanisms for the longevity of vaccine-induced antibody.

Discussion: The results of this trial are likely to directly impact WHO recommendations on whether booster vaccination is required for children in endemic areas, and if so, the optimal timing of such a booster.

Keywords: Children; Clinical trial; Global Health; The Gambia; WHO guidelines; Yellow Fever; booster; vaccine.

Plain language summary

Why is it important?: Yellow fever is a potentially deadly disease that is found across sub-Saharan Africa and South America. Fortunately, an effective vaccine exists and is used in affected countries to protect children and adults against the disease. Current World Health Organization (WHO) guidelines recommend that a single vaccination is sufficient to provide life-long protection. However, recent data show that many children who are vaccinated when they are very young (especially under the age of 12 months) have decreasing immune responses over time, meaning they may become vulnerable to yellow fever again as they get older.

Research overview: This study aims to understand whether children who were vaccinated against yellow fever when they were very young require a booster dose of the vaccine, and if so, at which age this booster dose should be given. This study was conducted by the Medical Research Council unit in The Gambia, in West Africa, from 2022 to 2024. Children who were vaccinated against yellow fever at 9–10 months of age as part of the normal childhood vaccination schedule were recruited with parental consent. Three different cohorts of children were included and given yellow fever boosters at ages 15 months, 4 years, or 8.5 years. The researchers tested the children’s antibody levels before and after the booster to understand how the children of different ages responded to the booster. The researchers could also compare their results against the children’s known antibody levels after their first vaccination to understand how these had changed over time.

Key takeaway: This research will help clinicians, scientists and policymakers better understand the decline of immune responses after primary yellow fever vaccination in early childhood and evaluate the need and optimal timing for a booster vaccine.

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Conflict of interest statement

No competing interests were disclosed.

Figures

Figure 1.
Figure 1.. Study design.
See this image and copyright information in PMC

References

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