Immunogenicity of a single dose of the 17DD yellow fever vaccine in a cohort of adults and children in a non-endemic area, and its association with dengue and Zika seropositivity

In 2013, the World Health Organization (WHO) withdrew the recommendation of booster doses of the yellow fever (YF) vaccine, based on retrospective and cross-sectional studies that showed lifelong protective immunity from a single dose. Currently, yellow fever transmission in Brazil occurs only through the jungle (sylvatic) cycle. However, the high vector density of Aedes aegypti, which transmits other orthoflaviviruses, is a concern for the expansion of YF in other regions of the country. We conducted a cohort study to assess the duration of vaccine-induced immunity in adults and children residing in an area without wild-type YF virus circulation but with a high incidence of other orthoflaviviruses. This phase IV, uncontrolled cohort study was conducted in three municipalities in northeastern Brazil. The 17DD strain vaccine was administered to children aged 9 months to 4 years and adults aged 18 to 50 years. Blood samples for antibody titration were collected before vaccination, 30-45 days after, and one year after vaccination. The following assays were used: µFRNT for yellow fever and dengue; PRNT for Zika; and chemiluminescence for Zika (IgG and IgM) and dengue (IgG). YF seroconversion rates 30-45 days post-vaccination increased with age, reaching 99% in adults, while 10% of infants remained without detectable antibodies. Seropositivity for dengue neutralizing antibodies was inversely associated with YF antibody titers 30-45 days post-vaccination. Previous Zika infection showed no substantial association with YF antibody titers post-vaccination. One year after vaccination, a considerable reduction in YF antibody titers was observed across all age groups, regardless of prior dengue or Zika infections. Our data support the Brazilian National Immunization Program's recommendation for a booster dose of the vaccine at 4 years of age. Current recommendations assuming lifelong protection from a single dose of the YF vaccine do not appear to provide sufficient protection in high-risk areas, particularly where infants are the primary target for vaccination.