Non- inferiority fractional-doses trial for yellow fever vaccine (NIFTY)

The NIFTY trial aims to determine the immunogenicity of reduced doses of Yellow Fever vaccine in comparison to that of the full vaccine dose in Kenyan and Ugandan adults and children.

Yellow fever (YF) is a disease caused by a mosquito-borne flavivirus that is endemic in sub-Saharan Africa and tropical South America. YF virus infection can cause mild or severe illness, leading to jaundice, kidney failure, bleeding and death. The YF vaccine is shown to be very effective for disease control, including prevention of YF outbreaks. However insufficient vaccine is produced for routine use, and whilst a YF vaccine stockpile is reserved for outbreak control, this is frequently depleted. Measures to increase the global supply of YF vaccine are urgently needed.

To address this, the World Health Organization (WHO) has recommended consideration of using fractions of standard YF vaccine dose to be able to vaccinate more individuals with a given quantity of vaccine in outbreak situations when there are insufficient doses to vaccinate the population at risk. However, the actual minimal dose of YF vaccine needed to elicit an immune response has not been determined. In this study, we will assess whether the immune response and adverse events occurring after vaccination of adults and children with the standard full dose of YF vaccine are comparable to those observed after vaccination with one of three lower doses of vaccine, aiming to establish a minimal dose. Further, to support the implementation of a future YF control strategy using lower doses of vaccine, we will evaluate the views and perceptions of different stakeholders involved in national or international vaccine policy regarding the use of lower doses of the YF vaccine.

The study will take place in Kilifi, Kenya and Mbarara, Uganda among 480 healthy adults and 420 children who have previously not had the YF vaccine and/or YF infection and have no contraindications for vaccination. If any of the lower YF vaccine doses safely elicits immune response that are comparable to the full vaccine dose, then in effect this finding could have an impact on the number of doses that are produced, and substantially increase the number of doses that can be given based on the world’s currently available vaccine stock, and thereby enhance our ability to prevent and control YF outbreaks. The results from the interviews and discussions with vaccine policy stakeholders will support the development of a strategy to implement the use of lower YF vaccine doses for disease control.

 

Trial Teams

KEMRI Wellcome Trust Research Programme – Kilifi  Team

 

Epicentre – Mbarara Team

 

Institut Pasteur de Dakar Team

 

Clinical trial sites

Kilifi Kenya

Mbarara Uganda

NIFTY Consortium

Uganda Virus Research Institute  https://www.mrcuganda.org/

MSF Epicentre https://www.epicentre.msf.org/en

University of Oxford https://www.ox.ac.uk/

Institut Pasteur de Dakar https://www.pasteur.sn/

This project is part of the EDCTP2 programme supported by the European Union

https://www.edctp.org/