Immunogenicity of Fractional One-fifth and One-half Doses of Yellow Fever Vaccine Compared to Full Dose in Children 9-23 Months Old

NCT03725618 | Completed Phase 4

• 1 other identifier: 2017-197
• Study Type: interventional
• Target: 1,788
• Locations: 1 country
• Sites: 1

Brief Summary

A randomized clinical trial comparing fractional dose Yellow Fever vaccination to the full dose among children aged 9-23 months in Uganda. Children will have immune response assessed at baseline, 4 weeks, and 12 months after vaccination. Enrolled participants will be randomized to one of three arms: A. One-fifth fractional dose (0.1 ml) administered subcutaneously B. One-half fractional dose (0.25 ml) administered subcutaneously C. Full dose (0.5 ml) administered subcutaneously

Conditions

Yellow Fever

Outcome Measures

Primary Outcomes (1)

• Immune response at 4 weeks in terms of seroconversion following vaccination

  Assess whether seroconversion following one-fifth (0.1 ml) and one-half (0.25 ml) doses of YF 17DD vaccine is non-inferior to seroconversion following a full dose (0.5 ml) at 4 weeks post-vaccination in children aged 9 - 23 months. Study endpoints at 4 weeks will be the following: Seroconversion will be defined as seronegative participants (plaque reduction neutralization test with a 50% cut-off (PRNT50) \< 10) at enrollment who become seropositive (PRNT50 ≥ 10) at 4 week follow-up. A boosted response will be defined as baseline-positive participants who demonstrate a four-fold or greater change in YF virus-specific titers between the baseline and 4 week specimens, e.g. a change from 1:20 to 1:80.

  4 weeks post vaccination

Secondary Outcomes (1)

• Immune response at 12 months in terms of seroconversion following vaccination

  12 months post vaccination

Other Outcomes (2)

• Titers at 4weeks and 12 months

  4 weeks and 12 months

• Frequency of adverse events following vaccination

  1 hour, 3 days, 14 days, 28 days

Study Arms (3)

One-fifth fractional dose

EXPERIMENTAL

One-fifth fractional dose (0.1 ml) of Yellow Fever 17DD Vaccine administered subcutaneously

Biological: Yellow Fever 17DD Vaccine

One-half fractional dose

EXPERIMENTAL

One-half fractional dose (0.25 ml) of Yellow Fever 17DD Vaccine administered subcutaneously

Biological: Yellow Fever 17DD Vaccine

Full dose

EXPERIMENTAL

Full dose (0.5 ml) of Yellow Fever 17DD Vaccine administered subcutaneously

Biological: Yellow Fever 17DD Vaccine

Interventions

Yellow Fever 17DD Vaccine BIOLOGICAL

live attenuated vaccine based on the 17DD strain

Full dose; One-fifth fractional dose; One-half fractional dose

Eligibility Criteria

• Age: 9 Months - 23 Months
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Child (0-17)

You may qualify if:

• Age 9 to 23 months at the time of enrollment
• Intent to stay in the health center catchment area and availability to do study visits at 2 weeks, 4 weeks, and 12 months after enrollment date
• Informed consent signed by parent/guardian for child's participation in the study, including blood sample collections at 4 week and 12 month visits post-vaccination
• Willingness of parent/guardian to be contacted by study personnel by telephone and through home visits if they cannot be reached by telephone.

You may not qualify if:

• Verbal or written report of previous vaccination against YF
• Verbal or documented history of YF disease
• Contraindication for YF vaccine including:
• Allergy to eggs, gelatin, or neomycin
• Severe immune deficiency immunological including symptomatic HIV infection and HIV- infected persons with CD4 T-cell counts ≤200 cells/ mm³, primary immunodeficiencies, having received immunosuppressive doses of oral or injectable corticosteroids (or equivalent), having received immunomodulatory or chemotherapeutic agents
• Thymus disorder
• History of malignant neoplasm or recent hematopoietic stem cell transplantation
• Administration of immunoglobulins or other blood derivative within 6 months of enrollment in the study or during the study
• a. Exception: children with a history of Kawasaki disease who received gammaglobulin cannot be enrolled if they received it in the previous 11 months.
• Administration of any other attenuated viral vaccine in the month prior to enrollment, or if the administration of any other attenuated viral vaccine is expected during the month after enrollment. Note: the administration of measles vaccine on the same day as YF vaccination is not a contraindication; however, if Uganda introduces measles-rubella vaccine (MR), participants will not be able to receive MR on the same day as YF vaccine due to possible interference between rubella and YF vaccine. In this situation, children will have to delay study enrollment until 1 month after MR vaccination.
• Participating in another clinical drug trial of a drug, vaccine, or medical device
• Severely underweight defined as ≤ 3rd percentile in the height/weight tables
• Severe reaction to prior vaccination
• Any chronic or other condition that, in the opinion of the study staff, represents a health risk to the participant or interferes with the evaluation of the response to the vaccine

Sponsors & Collaborators

• Centers for Disease Control and Prevention: lead
• Infectious Disease Institute, Kampala, Uganda: collaborator
• MRC/UVRI and LSHTM Uganda Research Unit: collaborator
• Ministry of Health, Uganda: collaborator

Study Sites (1)

Centers for Disease Control and Prevention

Atlanta, Georgia, 30333, United States

Location

Related Publications (2)

• Casey RM, Harris JB, Ahuka-Mundeke S, Dixon MG, Kizito GM, Nsele PM, Umutesi G, Laven J, Kosoy O, Paluku G, Gueye AS, Hyde TB, Ewetola R, Sheria GKM, Muyembe-Tamfum JJ, Staples JE. Immunogenicity of Fractional-Dose Vaccine during a Yellow Fever Outbreak - Final Report. N Engl J Med. 2019 Aug 1;381(5):444-454. doi: 10.1056/NEJMoa1710430. Epub 2018 Feb 14.

  PMID: 29443626 BACKGROUND

• Lee SE, Najjengo M, Shaum A, Sekiziyivu AB, Carlock G, Casey RM, Lubega I, Tumwine C, Twinomuhwezi-Oyet E, Nakato WN, Sciarratta CN, Hyde TB, Chu SY, Doshi RH, Kambugu A, Gidudu JF. Adverse events following immunization (AEFI) with fractional one-fifth and one-half doses of yellow fever vaccine compared to standard dose in children 9-23 months old in Uganda, 2019-2022 - final report. Vaccine. 2026 Jan 8;74:128131. doi: 10.1016/j.vaccine.2025.128131. Online ahead of print.

  PMID: 41512502 DERIVED

MeSH Terms

Conditions

Yellow Fever

Condition Hierarchy (Ancestors)

Mosquito-Borne Diseases; Vector Borne Diseases; Infections; Arbovirus Infections; Virus Diseases; Flavivirus Infections; Flaviviridae Infections; RNA Virus Infections; Hemorrhagic Fevers, Viral

Study Design

• Study Type: interventional
• Phase: phase 4
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: PREVENTION
• Intervention Model: PARALLEL
• Sponsor Type: FED
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: October 12, 2018
• First Posted: October 31, 2018
• Study Start: November 1, 2018
• Primary Completion: September 1, 2021
• Study Completion: September 1, 2021
• Last Updated: April 8, 2025

Record last verified: 2025-04

Data Sharing

• IPD Sharing: Will not share

Locations

US (1)