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

Lancet Infect Dis. 2024 Jun;24(6):611-618. doi: 10.1016/S1473-3099(23)00809-5. Epub 2024 Feb 6.

Abstract

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 [0·1 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 (PRNT50). Participants with a PRNT50 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 (95·2%, 95% CI 93·2-96·7) participants were seropositive, including 361 (94·3%, 91·5-96·2) of 383 who were seronegative and 178 (97·3%, 93·8-98·8) 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.

Funding: Gavi, the Vaccine Alliance through the CDC Foundation.

Translation: For the French translation of the abstract see Supplementary Materials section.

MeSH terms

  • Adolescent
  • Adult
  • Antibodies, Neutralizing / blood
  • Antibodies, Viral* / blood
  • Child
  • Child, Preschool
  • Democratic Republic of the Congo / epidemiology
  • Disease Outbreaks* / prevention & control
  • Female
  • Humans
  • Male
  • Middle Aged
  • Prospective Studies
  • Vaccination
  • Yellow Fever Vaccine* / administration & dosage
  • Yellow Fever Vaccine* / immunology
  • Yellow Fever* / epidemiology
  • Yellow Fever* / immunology
  • Yellow Fever* / prevention & control
  • Yellow fever virus / immunology
  • Young Adult

Substances

  • Yellow Fever Vaccine
  • Antibodies, Viral
  • Antibodies, Neutralizing