Non- Inferiority Fractional-doses Trial for Yellow Fever Vaccine

Summary

In the recent past there has been a number of large urban Yellow Fever outbreaks in sub-Saharan Africa, tropical South Americas, The demand for Yellow Fever vaccines in response to the large urban outbreaks occurring concurrently and the risk of further spread through Africa and to Asia was larger than the available global supply. In this situation, the World Health Organisation (WHO) developed recommendations for the use of fractional doses of Yellow Fever vaccine as a dose-sparing strategy. These recommendations were based on data from a limited number of clinical trials, none of which had been conducted in Africa. This was due to the uncertainties on the minimum dose requirement. Our study complements a study which is comparing full standard dose to 1/5th of standard dose of all four WHO-prequalified YF vaccines in adults (ClinicalTrials.gov number: NCT02991495), and is currently ongoing at KEMRI CGMRC and Epicentre, Mbarara which is designed to answer questions on the use of current stock of YF vaccines with a potency as close as possible to each manufacturers' minimum release. Data from this trial will inform a WHO recommendation on using 1/5th of the current standard dose of vaccine for outbreak control. However, since many vials will contain excess YF vaccine such that 1/5th of a vial is likely to be substantially above the current minimum potency requirements, these data may not be scientifically explanatory regarding the minimum dose required for preventive use. The new complementary study, aims to determine the lowest YF vaccine dose that is non-inferior to the current standard full dose among populations in sub-Saharan Africa. The study will be conducted in Kenya (KEMRI Center for Geographical Medicine Research-Coast (CGMR-C), Kilifi) and Uganda (Epicentre, Mbarara) with trial participants recruited at both sites, using vaccine from one WHO-prequalified manufacturer (Institut Pasteur de Dakar, Senegal (IPD)).

Timeline

Start

2019-11-11

Primary completion

2020-03-30

Completion

2023-06-24

Publications

• Kimathi D, Juan-Giner A, Bob NS, Orindi B, Namulwana ML, Diatta A, Cheruiyot S, Fall G, Dia M, Hamaluba MM, Nyehangane D, Karanja HK, Gitonga JN, Mugo D, Omuoyo DO, Hussein M, Oloo E, Kamau N, Wafula J, Bendera J, Silvester N, Mwavita J, Joshua M, Thuranira JM, Agababyona C, Ngetsa C, Aisha N, Moki F, Buluku T, Munene M, Mwanga-Amumpaire J, Lutwama J, Kayiwa J, Kamaara E, Barrett AD, Kaleebu P, Bejon P, Sall AA, Grais RF, Warimwe GM. Low-dose yellow fever vaccination in infants: a randomised, double-blind, non-inferiority trial. Lancet. 2026 Jan 31;407(10527):497-504. doi: 10.1016/S0140-6736(25)02069-0. Epub 2026 Jan 13.
• Kimathi D, Juan-Giner A, Bob NS, Orindi B, Namulwana ML, Diatta A, Cheruiyot S, Fall G, Dia M, Hamaluba MM, Nyehangane D, Karanja HK, Gitonga JN, Mugo D, Omuoyo DO, Hussein M, Oloo E, Kamau N, Wafula J, Bendera J, Silvester N, Mwavita J, Joshua M, Mwendwa J, Agababyona C, Ngetsa C, Aisha N, Moki F, Buluku T, Munene M, Mwanga-Amumpaire J, Lutwama J, Kayiwa J, Kamaara E, Barrett AD, Kaleebu P, Bejon P, Sall AA, Grais RF, Warimwe GM; NIFTY Investigators. Low-Dose Yellow Fever Vaccine in Adults in Africa. N Engl J Med. 2025 Feb 20;392(8):788-797. doi: 10.1056/NEJMoa2407293.
• Kimathi D, Juan A, Bejon P, Grais RF, Warimwe GM; YEFE and NIFTY vaccine trials teams. Randomized, double-blinded, controlled non-inferiority trials evaluating the immunogenicity and safety of fractional doses of Yellow Fever vaccines in Kenya and Uganda. Wellcome Open Res. 2019 Nov 20;4:182. doi: 10.12688/wellcomeopenres.15579.1. eCollection 2019.

Drugs

Indications