Immunological response to fractional-dose yellow fever vaccine administered during an outbreak in Kinshasa, Democratic Republic of the Congo: results 5 years after vaccination from a prospective cohort study

Background In 2016, outbreaks of yellow fever in Angola and the Democratic Republic of the Congo led to a global vaccine shortage. A fractional dose of 17DD yellow fever vaccine (containing one-fifth [0<middle dot>1 ml] of the standard dose) was used during a pre-emptive mass campaign in August, 2016, in Kinshasa, Democratic Republic of the Congo among children aged 2 years and older and non -pregnant adults (ie, those aged 18 years and older). 1 year following vaccination, 97% of participants were seropositive; however, the long-term durability of the immune response is unknown. We aimed to conduct a prospective cohort study and invited participants enrolled in the previous evaluation to return 5 years after vaccination to assess durability of the immune response. Methods Participants returned to one of six health facilities in Kinshasa in 2021, where study staff collected a brief medical history and blood specimen. We assessed neutralising antibody titres against yellow fever virus using a plaque reduction neutralisation test with a 50% cutoff (PRNT 50 ). Participants with a PRNT 50 titre of 10 or higher were considered seropositive. The primary outcome was the proportion of participants seropositive at 5 years. Findings Among the 764 participants enrolled, 566 (74%) completed the 5 -year visit. 5 years after vaccination, 539 (95<middle dot>2%, 95% CI 93<middle dot>2-96<middle dot>7) participants were seropositive, including 361 (94<middle dot>3%, 91<middle dot>5-96<middle dot>2) of 383 who were seronegative and 178 (97<middle dot>3%, 93<middle dot>8-98<middle dot>8) of 183 who were seropositive at baseline. Geometric mean titres (GMTs) differed significantly across age groups for those who were initially seronegative with the lowest GMT among those aged 2-5 years and highest among those aged 13 years and older. Interpretation A fractional dose of the 17DD yellow fever vaccine induced an immunologic response with detectable titres at 5 years among the majority of participants in the Democratic Republic of the Congo. These findings support the use of fractional-dose vaccination for outbreak prevention with the potential for sustained immunity.