Anna H.E. Roukens, MD, PhD *; Karlijn van Halem, MD *; Adriëtte W. de Visser, BSc; Leo G. Visser, MD, PhD
Acknowledgment: The authors thank the participants who kindly provided a blood sample 10 years after the initial trial. They also thank Ann Vossen for her help in performing the PRNT and Jacco Wallinga for his help with the statistical analysis.
Financial Support: By the Department of Infectious Diseases at LUMC and a research grant from the International Society of Travel Medicine.
Disclosures: Dr. Visser reports reimbursement of travel expenses from GlaxoSmithKline outside the submitted work. Authors not named here have disclosed no conflicts of interest. Disclosures can also be viewed at www.acponline.org/authors/icmje/ConflictOfInterestForms.do?msNum=M18-1529.
Editors' Disclosures: Christine Laine, MD, MPH, Editor in Chief, reports that her spouse has stock options/holdings with Targeted Diagnostics and Therapeutics. Darren B. Taichman, MD, PhD, Executive Editor, reports that he has no financial relationships or interests to disclose. Cynthia D. Mulrow, MD, MSc, Senior Deputy Editor, reports that she has no relationships or interests to disclose. Deborah Cotton, MD, MPH, Deputy Editor, reports that she has no financial relationships or interest to disclose. Jaya K. Rao, MD, MHS, Deputy Editor, reports that she has stock holdings/options in Eli Lilly and Pfizer. Sankey V. Williams, MD, Deputy Editor, reports that he has no financial relationships or interests to disclose. Catharine B. Stack, PhD, MS, Deputy Editor for Statistics, reports that she has stock holdings in Proctor & Gamble, Pfizer, and Johnson & Johnson.
Reproducible Research Statement:Study protocol: See the . Statistical code and data set: Not available.
Corresponding Author: Anna H.E. Roukens, MD, PhD, Department of Infectious Diseases, C5-P, Leiden University Medical Center, Albinusdreef 2, 2333 ZA Leiden, the Netherlands; e-mail, A.H.E.Roukens@lumc.nl.
Current Author Addresses: Drs. Roukens, van Halem, and Visser and Ms. de Visser: Department of Infectious Diseases, C5-P, Leiden University Medical Center, Albinusdreef 2, 2333 ZA Leiden, the Netherlands.
Author Contributions: Conception and design: A.H.E. Roukens, L.G. Visser.
Analysis and interpretation of the data: A.H.E. Roukens, K. van Halem, A.W. de Visser, L.G. Visser.
Drafting of the article: A.H.E. Roukens, K. van Halem, L.G. Visser.
Critical revision of the article for important intellectual content: A.H.E. Roukens, K. van Halem, L.G. Visser.
Final approval of the article: A.H.E. Roukens, K. van Halem, A.W. de Visser, L.G. Visser.
Provision of study materials or patients: K. van Halem.
Statistical expertise: A.H.E. Roukens, A.W. de Visser, L.G. Visser.
Obtaining of funding: A.H.E. Roukens.
Administrative, technical, or logistic support: A.H.E. Roukens, K. van Halem, A.W. de Visser.
Collection and assembly of data: A.H.E. Roukens, K. van Halem, A.W. de Visser.
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.
To evaluate whether fractional-dose vaccination can confer long-term immunity.
10-year follow-up of a subgroup of a randomized, controlled, noninferiority trial. (Dutch Trial Register: NTR7094 [current study] and ISRCTN46326316 [original study])
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.
Virus-neutralizing antibody responses were measured by a plaque reduction neutralization test.
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.
Only 48% of participants from the original trial participated in this study.
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.
Leiden University Medical Center and the International Society of Travel Medicine.
Roukens AH, van Halem K, de Visser AW, Visser LG. Long-Term Protection After Fractional-Dose Yellow Fever Vaccination: Follow-up Study of a Randomized, Controlled, Noninferiority Trial. Ann Intern Med. ;169:761–765. doi: 10.7326/M18-1529
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Published: Ann Intern Med. 2018;169(11):761-765.
Published at www.annals.org on 27 November 2018
Infectious Disease, Prevention/Screening, Vaccines/Immunization.
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