Yellow Fever

Thursday 1 July 2021 - Updated on Tuesday 10 June 2025
Learn about Epicentre's ongoing yellow fever studies.

Fractional doses: YF vaccine

Although yellow fever (YF) vaccine is highly effective, global supply shortages constrain vaccination activities, and particularly outbreak response. During large epidemics affecting Angola and the Democratic Republic of Congo (DRC) in 2016, WHO recommended the consideration of fractional dosing as a dose-sparing strategy to protect the population at risk. Nevertheless, evidence supporting this recommendation was limited and WHO called for additional research. 

YEFE

The YEFE trial aimed to generate the data needed to recommend fractional doses (i.e. 1/5th) of any WHO prequalified YF vaccine to be used in emergency situations when there are insufficient standard doses to protect the population at risk. This was a double-blind randomized controlled trial that assessed the immunological non-inferiority and safety of a fractional dose compared to standard dose for each of the four WHO pre-qualified YF vaccines in adults, children aged 9 to 59 months of age and HIV+ adults. Immunogenicity was assessed by PRNT50 at 10 days, 28 days and 1-year post-vaccination. Laboratory analyses were conducted at Institut Pasteur Dakar, Senegal. 

This study was implemented in 2017 and 2020 in Mbarara, Uganda, and Kilifi, Kenya.

The results have helped to extend WHO recommendation on the use of fractional dosing. 

 

Country

Uganda, Kenya

Status

Completed

Publication on adult population

Publication on children 

Publication on HIV+ adults

Our Role

Sponsor, Scientific Oversight, Study site

 

NIFTY

To complement the results provided by the YEFE trial, the NIFTY trial aimed to determine the lowest vaccine dose that would elicit an adequate immune response. This was a double-blind randomized controlled trial that assessed the immunological non-inferiority and safety of lower doses compared to standard of the yellow fever vaccine manufactured by Institut Pasteur Dakar, Senegal. Three low doses were assessed in adults (1000, 500 and 250 IU/dose). The lowest dose determined as non-inferior in adults was assessed in children aged 9 to 12 months co-administered with the measles and rubella containing vaccine. Immunogenicity was assessed by PRNT50 at 10 days, 28 days and 1-year post-vaccination. Laboratory analyses were conducted at Institut Pasteur Dakar, Senegal. 

This study was implemented by Epicentre Mbarara and KEMRI-Wellcome Trust research Programme in Kilifi, Kenya between 2019 and 2023. The results inform about minimum dose requirements in adults and children and further support the extension of WHO recommendation on the use of fractional dosing. 

Country

Uganda, Kenya

Status

Completed

Publication on adult population

Our Role

Scientific Oversight, Study Site

 

Durability of the immune response 

Following the implementation of the YEFE and NIFTY trial this study aims to extend the evidence of fractional dosing of YF vaccines for policy impact. The durability of the protective immune response following fractional dosing remains unknown. Moreover, there are conflicting data on durability in children for both full and fractional doses. This cross-sectional study aims to determine YF neutralizing antibody levels in adults and children who participated in the YEFE and NIFTY studies and combine these data with data from infants from an ongoing non-inferiority fractional dosing trial in The Gambia. 

The study will provide information on immune protection 2 to 8 years post-vaccination, determining the durability of the immunity induced by fractional dosing and providing information on need of booster vaccination. 

This study is implemented by Epicentre Mbarara, KEMRI-Wellcome Trust research Programme in Kilifi, Kenya and the Medical Research Council Unit The Gambia. 

Country

Uganda, Kenya, The Gambia

Status

In preparation, not yet started

Our Role

Scientific Oversight, Study Site

To find out more about this issue

https://www.thelancet.com/journals/langlo/article/PIIS2214-109X(23)00594-6/fulltext

https://www.thelancet.com/journals/laninf/article/PIIS1473-3099(24)00008-2/abstract

 

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