Yellow fever (YF) is a mosquito-borne viral disease 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 outbreak control as well as for the prevention of outbreaks. However insufficient vaccine is produced for routine use, and the stockpile of reserved for outbreak control is frequently depleted.
The trial aims to compare the safety and immune response of the normal full and reduced doses of yellow fever vaccine in adults and children. The World Health Organisation (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. We will compare the immune response and adverse events after vaccination using a standard dose of YF vaccine versus the response after one of three low doses of vaccine.
The study will take place in Kilifi, Kenya and Mbarara, Uganda among healthy HIV negative adults and children. In total, 1680 adults (840 at each site) and 1060 children aged 9 months to 5 years (530 at each site) will be included.
Participants who have previously not had the YF vaccine and/or YF infection will be screened for any significant health problems, then receive a single dose of YF vaccine. Participants will then need to attend follow up to have blood tests for antibody levels, to show immune responses to the vaccine, and to be asked about any side effects.
The risks relate to the possibility of developing an allergic or other reaction upon administration of the YF vaccine. There are no immediate health benefits to individuals participating in this study other than information about their health. If there was a YF outbreak in the future, then participants getting full dose would be expected to be protected and there is a chance that participants who receive the lower dose would be protected against infection. We are not able to issue YF vaccination certificates to participants or provide reassurance regarding protection. Once we have unblinded the study we will be able to reassure those receiving full dose that they are protected, and if we see no less or comparable protection then we will be able to reassure those receiving lower vaccine doses regarding protection for at least two years. The laboratory testing of immunological response is not intended to provide reassurance on an individual-by-individual basis and we would not provide individual-level immunological data to participants.
If any of the low YF vaccine doses raises the same immune response as a full dose, then in effect this finding will substantially increase the number of doses that can be given based on the world’s currently available vaccine stock and will enhance our ability to prevent and control YF outbreaks.The study will start upon receipt of ethical clearance. Data collection, analysis and write up will take place over 40 months.