Fractional-Dose Yellow Fever Vaccination Provides Long-Term Protection

November 28, 2018

By Will Boggs MD

NEW YORK (Reuters Health) - Primary vaccination with one-fifth the standard dose of yellow fever vaccine provides at least 10 years of protection against the virus, researchers report.

"We already measured the immune response against fractional-dose yellow fever vaccination one year after the vaccination (published in 2008) and did not expect the immune response to develop differently after that time," Dr. Anna H. E. Roukens from Leiden University Medical Center, in the Netherlands, told Reuters Health by email. "Nevertheless, long-term protection needed to be confirmed in order to have more confidence in fractional-dose yellow fever vaccination."

Although fractional-dose yellow fever vaccine has been used successfully to increase vaccine coverage in outbreaks in Kinshasa and in Brazil, the World Health Organization (WHO) recently concluded that this approach does not meet the requirements of the International Health Regulations, concluding that proof of vaccination for international travel requires re-vaccination with a standard full dose "until long-term protection is better documented."

Dr. Roukens and colleagues investigated the neutralizing antibody response in 75 of the original 155 participants 10 years after they received the vaccine during a randomized noninferiority trial.

Overall, 73 of these 75 participants had seroprotective antibody levels 10 years after primary vaccination, including 98% (39/40) of participants who received the intradermal fractional dose of the vaccine and 97% (34/35) of those who received the subcutaneous standard dose, the team reports in the Annals of Internal Medicine, online November 27.

Mean geometric mean titers did not differ significantly between the fractional-dose and full-dose participants.

"These findings reinforce the policy of using fractional doses in preventive mass vaccination campaigns before an impending outbreak and show that a booster dose of 17D-YFV vaccine is not necessary after receipt of a fractional dose," the researchers conclude.

"If the minimum dose can be guaranteed by the manufacturer, even in circumstances where the cold-chain is not optimal for vaccine storage, there is no reason why the standard dose could not be changed to this effective fractional dose," Dr. Roukens said.

Dr. David Heymann from London School of Hygiene and Tropical Medicine, who was not involved in the study, told Reuters Health by email, "I did not find these results surprising - the same is true for other vaccines in fractional doses, such as the human rabies vaccine."

The vaccine "was used this way because of the evidence-based decision of WHO to recommend it at the time of shortage," he said. "In order for this to become standard, as I understand it, the manufacturers would need to submit new evidence to the regulatory agencies for a ruling from them."


Ann Intern Med 2018.

(c) Copyright Thomson Reuters 2018. Click For Restrictions -

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