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

2018 Feb 14. doi: 10.1056/NEJMoa1710430. [Epub ahead of print]

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

Author information

1
From the Institut National de Recherche Biomédicale (S.A.-M., P.M.N., G.M.K., J.-J.M.-T.), Division of Global Health Protection, Centers for Disease Control and Prevention (CDC) (A.S.G.), and Programme Elargi de Vaccination, Ministre de la Santé (G.K.M.S.) – all in Kinshasa, Democratic Republic of Congo; 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.), CDC, Atlanta; and Division of Vector-Borne Diseases, CDC, Fort Collins, CO (J.L., J.E.S.).

Abstract

Background 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. Methods 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 28 to 35 days after vaccination, using a plaque reduction neutralization test with a 50% cutoff (PRNT50). Participants with a PRNT50 titer of 10 or higher at baseline 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. Results Among 716 participants who completed 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). Conclusions A fractional dose of the 17DD yellow fever vaccine was effective at inducing seroconversion in most of the participants who were seronegative at baseline. 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.).

 Link to the abstract: https://www.ncbi.nlm.nih.gov/pubmed/29443626

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