Long-Term Protection After Fractional-Dose Yellow Fever Vaccination: Follow-up Study of a Randomized, Controlled, Noninferiority Trial

Background: Outbreaks of yellow fever and a frequently depleted vaccine stock increase demand for a dose-sparing strategy. A fractional dose of 17D yellow fever virus (17D-YFV) vaccine has been shown to be noninferior to the standard dose in inducing seroprotection.

Objective: To evaluate whether fractional-dose vaccination can confer long-term immunity.

Design: 10-year follow-up of a subgroup of a randomized, controlled, noninferiority trial. (Dutch Trial Register: NTR7094 [current study] and ISRCTN46326316 [original study]).

Setting: The Netherlands.

Participants: Seventy-five of 155 participants in the original trial provided a blood sample for this study. These 75 participants had received primary vaccination with 17D-YFV vaccine 10 years before. Forty received a 0.1-mL fractional dose intradermally, and 35 received the standard 0.5-mL dose subcutaneously.

Measurements: Virus-neutralizing antibody responses were measured by a plaque reduction neutralization test.

Results: Thirty-nine of 40 (98% [95% CI, 89% to 100%]) participants had protective levels of yellow fever-neutralizing antibodies more than 10 years after receiving a fractional dose of 17D-YFV vaccine compared with 34 of 35 (97% [CI, 87% to 100%]) in the standard-dose group.

Limitation: Only 48% of participants from the original trial participated in this study.

Conclusion: Intradermal administration of a one-fifth dose of yellow fever vaccine induced a protective immune response that lasted for 10 years after vaccination. Persons receiving a fractional dose of yellow fever vaccine do not require a booster vaccination for long-term protection against yellow fever.

Primary Funding Source: Leiden University Medical Center and the International Society of Travel Medicine.