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N Engl J Med. 2019 Aug 1;381(5):444-454. doi: 10.1056/NEJMoa1710430. Epub 2018 Feb 14.

Immunogenicity of Fractional-Dose Vaccine during a Yellow Fever Outbreak - Final Report.

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From the Global Immunization Division (R.M.C., J.B.H., M.G.D., G.U., G.P., T.B.H.) and the Epidemic Intelligence Service (R.M.C.), Centers for Disease Control and Prevention (CDC), Atlanta; Institut National de Recherche Biomédicale (S.A.-M., P.M.N., G.M.K., J.-J.M.-T.), Division of Global Health Protection (A.S.G.), Division of Global HIV and Tuberculosis (R.E.), CDC, and Programme Elargi de Vaccination, Ministère de la Santé (G.K.M.S.) - all in Kinshasa, Democratic Republic of Congo; and the Division of Vector-Borne Diseases, CDC, Fort Collins, CO (J.L., O.K., J.E.S.).



In 2016, the response to a yellow fever outbreak in Angola and the Democratic Republic of Congo led to a global shortage of yellow fever vaccine. As a result, a fractional dose of the 17DD yellow fever vaccine (containing one fifth [0.1 ml] of the standard dose) was offered to 7.6 million children 2 years of age or older and nonpregnant adults in a preemptive campaign in Kinshasa. The goal of this study was to assess the immune response to the fractional dose in a large-scale campaign.


We recruited participants in four age strata at six vaccination sites. We assessed neutralizing antibody titers against yellow fever virus in blood samples obtained before vaccination and at 1 month and 1 year after vaccination, using a plaque reduction neutralization test with a 50% cutoff (PRNT50). Participants with a PRNT50 titer of 10 or higher were considered to be seropositive. Those with a baseline titer of less than 10 who became seropositive at follow-up were classified as having undergone seroconversion. Participants who were seropositive at baseline and who had an increase in the titer by a factor of 4 or more at follow-up were classified as having an immune response.


Among 716 participants who completed the 1-month follow-up, 705 (98%; 95% confidence interval [CI], 97 to 99) were seropositive after vaccination. Among 493 participants who were seronegative at baseline, 482 (98%; 95% CI, 96 to 99) underwent seroconversion. Among 223 participants who were seropositive at baseline, 148 (66%; 95% CI, 60 to 72) had an immune response. Lower baseline titers were associated with a higher probability of having an immune response (P<0.001). Among 684 participants who completed the 1-year follow-up, 666 (97%; 95% CI, 96 to 98) were seropositive for yellow fever antibody. The distribution of titers among the participants who were seronegative for yellow fever antibody at baseline varied significantly among age groups at 1 month and at 1 year (P<0.001 for both comparisons).


A fractional dose of the 17DD yellow fever vaccine was effective at inducing seroconversion in participants who were seronegative at baseline. Titers remained above the threshold for seropositivity at 1 year after vaccination in nearly all participants who were seropositive at 1 month after vaccination. These findings support the use of fractional-dose vaccination for outbreak control. (Funded by the U.S. Agency for International Development and the Centers for Disease Control and Prevention.).

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