Yellow FeverPhase 4NIFTYNCT04059471
Non- Inferiority Fractional-doses Trial for Yellow Fever Vaccine
A Phase 4 study testing Yellow fever vaccine, Institut Pasteur in people with Yellow Fever, run by University of Oxford at 2 sites in 2 countries.
Trial 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… Read more about this study
- Who is it for?
- Ages 9 months to 59 yearsHealthy volunteers can take part
- Conditions the study is for
- Yellow Fever
- What is being tested?
- Yellow fever vaccine, Institut Pasteur
- Type of treatment
- Vaccines, Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 900 participants
- Where
- 2 sitesin 2 countries
- Study dates
- 11 Nov 2019to 24 Jun 2023
- Phase
- Phase 4
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 9 months to 59 years
- All sexes
- Healthy volunteers accepted
- Child, Adult
Who may be able to join
- Individuals aged ≥18 - <60 years of age.
- Children aged between 9 months and 12 months.
- HIV negative on serological screening OR HIV positive adults and children aged > 18 months on serological testing, and no symptoms suggestive of current clinical immunosuppression and cluster of differentiation-4 (CD4) count>200 (for adults) and CD4% > 25% (for children aged 9-12 months) within the last 6 months.
- Ability to provide informed consent to participate in the study
Who cannot join
- Known contraindications to YF vaccination such as allergies to egg protein and chicken products or any component of the vaccine (including gelatin, eggs, eggs products or chicken products), immunodeficiency, known thymus disorder, such as thymoma and myasthenia gravis
- Using corticosteroids or other immunosuppressive therapy
- Thymus disorder, such as thymoma and myasthenia gravis
- Acute febrile disease on the day of vaccination with temperature >37.5 degrees Celsius is a temporal contraindication.
- Previous YF vaccination
- Previous YF infection as determined from history
Show all 10Show fewer
- Pregnancy (as determined by a urine test on the proposed day of vaccination) and lactating women
- Planning to migrate out of the study areas before the end of the study follow-up
- Planning to travel to a country requiring YF vaccination certificate within the first year after vaccination.
- Any condition or criteria, including acute or chronic clinically significant abnormality that in the opinion of the investigator might compromise the wellbeing of the volunteer or interfere with the outcome of the study.
Trial locations and contacts
2 sites in 2 countries.
2 sites in 2 countries
About this study
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)).
Read the detailed description
Yellow fever (YF) is a disease caused by a mosquito-borne flavivirus that is endemic in sub-Saharan Africa and tropical South America. Ninety percent of YF cases are in Africa where YF virus is transmitted by different mosquito genera in three recognized transmission cycles. A sylvatic cycle involves transmission between forest-dwelling mosquitoes (Haemagogus spp) and non-human primate reservoirs, with sporadic incidental transmission to humans (e.g. forest workers). An intermediate cycle, occurring only in Africa, involves mosquito transmission between non-human primates and humans, or human-to-human transmission among humans living or working close to forested areas. An urban cycle involves transmission between humans and urban mosquito vectors, primarily Aedes aegypti, and occurs when a viraemic person, infected in the sylvatic or intermediate cycle, introduces YF virus to areas with a large non-immune population and A. aegypti vectors resulting in disease outbreaks.
Infection with YF virus is characterised by a wide range of manifestations, ranging from subclinical infection with mild and non-specific symptoms, to severe, life-threatening illness with jaundice, renal failure and haemorrhage.
A highly effective vaccine is available for use against YF in adults and children aged ≥9 months. The vaccine is a freeze-dried preparation of live attenuated YF virus strain 17D, which was developed in 1937 and is produced by four WHO-prequalified manufacturers. A single dose of YF vaccine is considered sufficient to confer life-long protective immunity against all seven known genotypes of wild-type YF virus. Protective levels of YF virus neutralizing antibodies are developed in 80-100% vaccine recipients within 10 days after vaccination, and in 99% within a month.
Although fractional dosing has recently been used in vaccination campaigns in Kinshasa and Brazil in 2016, 2017 and 2018, WHO recommendations were based on a limited number of clinical studies and important data gaps remain.
fractional vaccine dosing is compounded by the uncertainty surrounding minimum dose requirements.
This study therefore aims to determine the lowest dose in International Units (IU/dose) that is non-inferior to the standard full dose among populations in sub-Saharan Africa. The data generated in this study will provide information regarding the re-definition of the minimal dose and potency requirements of the vaccine. The study will also provide further confidence in the use of fractional doses of YF vaccine during epidemics. In addition, the investigators will assess the range of views and perceptions of key stakeholders in vaccine policy and implementation on reduced vaccine dose usage during YF epidemics and for routine use.
. The study will be conducted at the KEMRI CGMRC in Kilifi, Kenya and at Epicentre in Mbarara, Uganda. Both these sites are already working together in an ongoing study (ClinicalTrials.gov number: NCT02991495).
Adult participants (n=480) will be randomized for vaccination with full standard dose or with 1000, 500 or 250 IU (i.e. 4 arms) with a 1:1:1:1 allocation ratio. Results for the safety and primary outcome of the adult study will then be reviewed by the DSMB, and the lowest non-inferior dose in the adult study selected for assessment in children aged 9 months to 5 years (n=420) in comparison to full standard dose (i.e. 2 arms) with a 1:1 allocation ratio. The determination of the non-inferior dose to use in children will be made by the sponsor in discussion with the study Data Safety and Monitoring Board (DSMB), vaccine manufacturer and relevant stakeholders, and the final decision communicated to the various regulatory authorities as a notification (i.e. Scientific and Ethics Review Board (SERU) at KEMRI, Oxford Tropical Research Ethics Committee (OxTREC) and Pharmacy and Poisons board (PPB) for the Kilifi site, Mbarara University of Science and Technology's Research Ethics Committee (MUST-REC), Uganda National Council of Science and Technology (UNCST) and National Drug Authority (NDA) for the Mbarara site).
Adult vaccinees will be followed up for 2 years, and children for 1 year. There will be no gradual age de-escalation on the basis that there are few safety concerns with the full dose of YF vaccines, having been used in millions of children worldwide.
- Conditions
- Yellow Fever
- Being tested
- Yellow fever vaccine, Institut Pasteur
- Keywords
- Yellow Fever vaccine, Fractional doses, Yellow Fever, Vaccine dose
- Medical subject headings
- Yellow Fever
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Yellow fever vaccine, Institut PasteurBiological
Also called Children sub-study
Full dose and 500IU/dose
| Study group | Role | What they receive |
|---|---|---|
| Standard Dose | Active comparator | Yellow fever vaccine, Institut Pasteur, standard dose as release by manufacturer will be administered subcutaneously once. Receives: Biological: Yellow fever vaccine, Institut Pasteur |
| Fractional dose (1000 IU/dose) | Experimental | Yellow fever vaccine, Institut Pasteur, will be titrated to about 1000IU/dose and administered subcutaneously once. Receives: Biological: Yellow fever vaccine, Institut Pasteur |
| Fractional dose (500 IU/dose) | Experimental | Yellow fever vaccine, Institut Pasteur, will be titrated to about 500IU/dose and administered once. Receives: Biological: Yellow fever vaccine, Institut Pasteur |
| Fractional dose (250 IU/dose) | Experimental | Yellow fever vaccine, Institut Pasteur, will be titrated to about 250IU/dose and administered once. Receives: Biological: Yellow fever vaccine, Institut Pasteur |
What is being measured
The primary outcome is the main question the study is designed to answer.
The proportion of vaccinees that seroconverts as measured by Plaque Reduction Neutralisation Test (PRNT-50)
PRNT-50 will be used to quantify functional antibodies by neutralisation of the virus
Measured: 28 days post vaccination
Secondary outcomes (7)
Duration of immunity as measured by PRNT
To describe the longevity of functional antibodies post-vaccination with the different doses as measured by PRNT
Measured: 10 days, 28 days, 1 year and 2 years (adults)
Change in the geometric mean fold of the antibody titre as measured by PRNT
To describe change in the geometric mean antibodies between baseline and 28 days after vaccination.
Measured: Baseline and 28 days after vaccination
Other flavivirus antibodies interference as tested by neutralisation tests
To measure the impact of antibodies to other flaviviruses (including dengue, West Nile and zika viruses) on the baseline sample on YF vaccine immunogenicity 28 days after vaccination by pairwise comparison.
Measured: Baseline and 28 days after vaccination
Post-vaccination viremia as measured by quantitative Polymerase Chain Reaction (PCR)
To assess post-vaccination control of viremia by different vaccine doses by sparse sampling
Measured: baseline, and on days 2, 3, 4, 5, 6, 7 and 10 after vaccination
Changes in cellular immunology
To determine the change in T and B cell immune responses between baseline and days post-vaccination
Measured: baseline and days 10 and 28 post-vaccination.
Changes in biomarkers
To determine the change in serum biomarkers levels (including, TNF, INF-γ, IL-2, IL-4, IL-5, IL-10, IL-8/CXCL-8, MCP-1/CCL-2, MIG/CXCL-9 and IP-10/CXCL-10) between baseline and post-vaccination by pairwise comparison.
Measured: Baseline, and on days 2, 3, 4, 5, 6, 7,10 and 28 after vaccination
Safety of different doses as described by the occurrence of adverse events (AE) and serious adverse events.
To assess the occurrence of adverse events (AE) over 28 days after vaccination and serious adverse events throughout the duration of the study.
Measured: 28 days after vaccination and an average of 1 year for the adult study and two years for the children study. .
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted16 Aug 2019
- Study start11 Nov 2019
- Primary completion30 Mar 2020
- Study completion24 Jun 2023
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (3)Papers the sponsor has linked to this study.
- Other trials for Yellow FeverStudies of the same condition, open and under way.
- More trials run by University of OxfordThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 4
- Primary purpose
- Prevention
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Model description
- Adult participants (n=480) will be randomized for vaccination with full standard dose or with 1000, 500 or 250 IU (i.e. 4 arms) with a 1:1:1:1 allocation ratio. Results for the safety and primary outcome of the adult study will then be reviewed by the DSMB, and the lowest non-inferior dose in the adult study selected for assessment in children aged 9 months to 5 years (n=420) in comparison to full standard dose (i.e. 2 arms) with a 1:1 allocation ratio.
- Masking
- Triple blind
- Who is masked
- Participant, Investigator, Outcomes assessor
- Enrolment
- 900 participants (actual)
Sponsor and investigators
- Lead sponsor
- University of Oxford
- Sponsor type
- University, hospital or other
- Collaborators
- KEMRI-Wellcome Trust Collaborative Research Program, Institut Pasteur, MRC/UVRI and LSHTM Uganda Research Unit, Epicentre, Paris, France and Mbarara University of Science and Technology, Faculty of Medicine, Mbarara, Uganda
- Responsible party
- Principal investigator, George Warimwe, PhD, University of Oxford
- Investigators
- Philip Bejon, PhD, Study director, University of Oxford
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT04059471
- Sponsor's protocol ID
- OxTREC Ref: 2-19
- Other IDs
- SERU 3797, HS 2596, MUREC 1/7, ECCT/19/03/04
- Acronym
- NIFTY
- Status last verified
- Feb 2024
- First submitted
- 26 Jul 2019
- Last updated
- 9 Feb 2024
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- No: Individual Participant Data will be de-identified and coded before sharing.
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.
PubMed 41544642Kimathi 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.
PubMed 39970397Kimathi 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.
PubMed 31984244
Study at a glance
From the registry record, last updated by the sponsor on 9 Feb 2024. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Non- Inferiority Fractional-doses Trial for Yellow Fever Vaccine
- ClinicalTrials.gov ID
- NCT04059471
- Acronym / sponsor ID
- NIFTY / OxTREC Ref: 2-19
- Conditions
- Yellow Fever
- Keywords
- Yellow Fever vaccine, Fractional doses, Yellow Fever, Vaccine dose
- Phase
- Phase 4
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 900 participants (actual)
- Lead sponsor
- University of OxfordUniversity, hospital or other
- Collaborators
- KEMRI-Wellcome Trust Collaborative Research Program, Institut Pasteur, MRC/UVRI and LSHTM Uganda Research Unit, Epicentre, Paris, France and Mbarara University of Science and Technology, Faculty of Medicine, Mbarara, Uganda
- Study start
- 11 Nov 2019 (actual)
- Primary completion
- 30 Mar 2020 (actual)
- Study completion
- 24 Jun 2023 (actual)
- First posted
- 16 Aug 2019 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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)).
Detailed description
Yellow fever (YF) is a disease caused by a mosquito-borne flavivirus that is endemic in sub-Saharan Africa and tropical South America. Ninety percent of YF cases are in Africa where YF virus is transmitted by different mosquito genera in three recognized transmission cycles. A sylvatic cycle involves transmission between forest-dwelling mosquitoes (Haemagogus spp) and non-human primate reservoirs, with sporadic incidental transmission to humans (e.g. forest workers). An intermediate cycle, occurring only in Africa, involves mosquito transmission between non-human primates and humans, or human-to-human transmission among humans living or working close to forested areas. An urban cycle involves transmission between humans and urban mosquito vectors, primarily Aedes aegypti, and occurs when a viraemic person, infected in the sylvatic or intermediate cycle, introduces YF virus to areas with a large non-immune population and A. aegypti vectors resulting in disease outbreaks.
Infection with YF virus is characterised by a wide range of manifestations, ranging from subclinical infection with mild and non-specific symptoms, to severe, life-threatening illness with jaundice, renal failure and haemorrhage.
A highly effective vaccine is available for use against YF in adults and children aged ≥9 months. The vaccine is a freeze-dried preparation of live attenuated YF virus strain 17D, which was developed in 1937 and is produced by four WHO-prequalified manufacturers. A single dose of YF vaccine is considered sufficient to confer life-long protective immunity against all seven known genotypes of wild-type YF virus. Protective levels of YF virus neutralizing antibodies are developed in 80-100% vaccine recipients within 10 days after vaccination, and in 99% within a month.
Although fractional dosing has recently been used in vaccination campaigns in Kinshasa and Brazil in 2016, 2017 and 2018, WHO recommendations were based on a limited number of clinical studies and important data gaps remain.
fractional vaccine dosing is compounded by the uncertainty surrounding minimum dose requirements.
This study therefore aims to determine the lowest dose in International Units (IU/dose) that is non-inferior to the standard full dose among populations in sub-Saharan Africa. The data generated in this study will provide information regarding the re-definition of the minimal dose and potency requirements of the vaccine. The study will also provide further confidence in the use of fractional doses of YF vaccine during epidemics. In addition, the investigators will assess the range of views and perceptions of key stakeholders in vaccine policy and implementation on reduced vaccine dose usage during YF epidemics and for routine use.
. The study will be conducted at the KEMRI CGMRC in Kilifi, Kenya and at Epicentre in Mbarara, Uganda. Both these sites are already working together in an ongoing study (ClinicalTrials.gov number: NCT02991495).
Adult participants (n=480) will be randomized for vaccination with full standard dose or with 1000, 500 or 250 IU (i.e. 4 arms) with a 1:1:1:1 allocation ratio. Results for the safety and primary outcome of the adult study will then be reviewed by the DSMB, and the lowest non-inferior dose in the adult study selected for assessment in children aged 9 months to 5 years (n=420) in comparison to full standard dose (i.e. 2 arms) with a 1:1 allocation ratio. The determination of the non-inferior dose to use in children will be made by the sponsor in discussion with the study Data Safety and Monitoring Board (DSMB), vaccine manufacturer and relevant stakeholders, and the final decision communicated to the various regulatory authorities as a notification (i.e. Scientific and Ethics Review Board (SERU) at KEMRI, Oxford Tropical Research Ethics Committee (OxTREC) and Pharmacy and Poisons board (PPB) for the Kilifi site, Mbarara University of Science and Technology's Research Ethics Committee (MUST-REC), Uganda National Council of Science and Technology (UNCST) and National Drug Authority (NDA) for the Mbarara site).
Adult vaccinees will be followed up for 2 years, and children for 1 year. There will be no gradual age de-escalation on the basis that there are few safety concerns with the full dose of YF vaccines, having been used in millions of children worldwide.
Study design
- Primary purpose
- Prevention
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Triple blind (participant, investigator, outcomes assessor)
- Number of arms
- 4
- Model description
- Adult participants (n=480) will be randomized for vaccination with full standard dose or with 1000, 500 or 250 IU (i.e. 4 arms) with a 1:1:1:1 allocation ratio. Results for the safety and primary outcome of the adult study will then be reviewed by the DSMB, and the lowest non-inferior dose in the adult study selected for assessment in children aged 9 months to 5 years (n=420) in comparison to full standard dose (i.e. 2 arms) with a 1:1 allocation ratio.
| Arm | Type | Receives |
|---|---|---|
| Standard Dose | Active comparator | Biological: Yellow fever vaccine, Institut PasteurYellow fever vaccine, Institut Pasteur, standard dose as release by manufacturer will be administered subcutaneously once. |
| Fractional dose (1000 IU/dose) | Experimental | Biological: Yellow fever vaccine, Institut PasteurYellow fever vaccine, Institut Pasteur, will be titrated to about 1000IU/dose and administered subcutaneously once. |
| Fractional dose (500 IU/dose) | Experimental | Biological: Yellow fever vaccine, Institut PasteurYellow fever vaccine, Institut Pasteur, will be titrated to about 500IU/dose and administered once. |
| Fractional dose (250 IU/dose) | Experimental | Biological: Yellow fever vaccine, Institut PasteurYellow fever vaccine, Institut Pasteur, will be titrated to about 250IU/dose and administered once. |
Who may qualify
- Ages
- 9 months to 59 years
- Sex
- All
- Healthy volunteers
- Accepted
- Age groups
- Child, Adult
Key inclusion criteria (4 listed)
- Individuals aged ≥18 - <60 years of age.
- Children aged between 9 months and 12 months.
- HIV negative on serological screening OR HIV positive adults and children aged > 18 months on serological testing, and no symptoms suggestive of current clinical immunosuppression and cluster of differentiation-4 (CD4) count>200 (for adults) and CD4% > 25% (for children aged 9-12 months) within the last 6 months.
- Ability to provide informed consent to participate in the study
Key exclusion criteria (10 listed)
- Known contraindications to YF vaccination such as allergies to egg protein and chicken products or any component of the vaccine (including gelatin, eggs, eggs products or chicken products), immunodeficiency, known thymus disorder, such as thymoma and myasthenia gravis
- Using corticosteroids or other immunosuppressive therapy
- Thymus disorder, such as thymoma and myasthenia gravis
- Acute febrile disease on the day of vaccination with temperature >37.5 degrees Celsius is a temporal contraindication.
- Previous YF vaccination
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Yellow fever vaccine, Institut PasteurAlso: Children sub-studyFull dose and 500IU/dose | Biological | Fractional dose (1000 IU/dose), Fractional dose (250 IU/dose), Fractional dose (500 IU/dose), Standard Dose |
Primary outcome
The proportion of vaccinees that seroconverts as measured by Plaque Reduction Neutralisation Test (PRNT-50)
Time frame: 28 days post vaccination
PRNT-50 will be used to quantify functional antibodies by neutralisation of the virus
7 secondary outcomes
Duration of immunity as measured by PRNT
Time frame: 10 days, 28 days, 1 year and 2 years (adults)
Change in the geometric mean fold of the antibody titre as measured by PRNT
Time frame: Baseline and 28 days after vaccination
Other flavivirus antibodies interference as tested by neutralisation tests
Time frame: Baseline and 28 days after vaccination
Post-vaccination viremia as measured by quantitative Polymerase Chain Reaction (PCR)
Time frame: baseline, and on days 2, 3, 4, 5, 6, 7 and 10 after vaccination
Changes in cellular immunology
Time frame: baseline and days 10 and 28 post-vaccination.
Changes in biomarkers
Time frame: Baseline, and on days 2, 3, 4, 5, 6, 7,10 and 28 after vaccination
Safety of different doses as described by the occurrence of adverse events (AE) and serious adverse events.
Time frame: 28 days after vaccination and an average of 1 year for the adult study and two years for the children study. .
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 9 Feb 2024.
- Derived from this study: PubMed 41544642Kimathi 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.
- Derived from this study: PubMed 39970397Kimathi 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.
- Derived from this study: PubMed 31984244Kimathi 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.
- Individual participant dataSharing planned: No. Individual Participant Data will be de-identified and coded before sharing.
Related trials for Yellow Fever
Recruiting
Assessment of Communication Interventions on Vaccination Knowledge and Acceptance
Vaccination Knowledge and Acceptance, Informed Vaccine-decision Making
Active, not recruitingPhase 3
A Phase III Control Study of the Safety and Immunogenicity of vYF in Pediatric Population
Yellow Fever Immunization
RecruitingPhase 4
Antibiotics and Vaccine Immune Responses Study
Vaccine Response Impaired
Active, not recruitingPhase 2
Study on an Investigational Yellow Fever Vaccine Compared With YF-VAX in Adults in the USA
Yellow Fever, Healthy Volunteers
Recruiting
Baseline Assessment of Skin Resident Memory T Cells in Healthy Unvaccinated Participants
Yellow Fever (Healthy Volunteers), Biopsy/Methods
Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Philip Bejon, PhD study director
University of Oxford
2 sites in 2 countries: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 4 study testing Yellow fever vaccine, Institut Pasteur in people with Yellow Fever, run by University of Oxford at 2 sites in 2 countries.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 4 inclusion and 10 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 9 Feb 2024. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 2 sites in Kenya, Uganda. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 4 studies take place after a treatment is approved, to learn more about its long-term benefits and risks in everyday use.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
The proportion of vaccinees that seroconverts as measured by Plaque Reduction Neutralisation Test (PRNT-50) (time frame: 28 days post vaccination). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT04059471, which also lists 3 linked publications.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 9 Feb 2024.