Immunogenicity and safety of fractional dose yellow fever vaccination: A systematic review and meta-analysis.

BACKGROUND

Recent upsurges in yellow fever outbreaks are increasing the demand for yellow fever vaccine, while enormously straining global vaccine supply. Fractional dose yellow fever vaccination is being considered as a dose-sparing strategy to address current vaccine shortages. This systematic review and meta-analysis aimed to assess the effects of fractional dose yellow fever vaccination, in comparison with those of standard dose vaccination.

METHODS

We registered this review on the International Prospective Register of Systematic Reviews (PROSPERO, registration number: CRD42018084214), developed the protocol in line with the Preferred Reporting Items for Systematic Review and Meta-Analyses Protocols (PRISMA-P) and synthesised the evidence in accordance with the Preferred Reporting Items for Systematic Review and Meta-Analyses (PRISMA). We stratified meta-analyses by vaccine dose.

RESULTS

We retrieved 2524 records from the literature search, eleven of them potentially eligible. From these studies, we included eight eligible trials, with a total of 2371 participants. Seroconversion rates at four to five weeks following vaccination were similar between participants who received standard doses and participants who received fractional doses containing one-third (547 participants: risk ratio [RR] 1.02, 95% confidence interval [CI] 1.00-1.04), one-fifth (155 participants: RR 1.00, 95% CI 0.98-1.03), one-tenth (890 participants: RR 0.99, 95% CI 0.96-1.01), and one-fiftieth (661 participants: RR 0.97, 95% CI 0.92-1.02) of the standard dose. However, the rates of seroconversion were substantially lower among participants who received fractional doses containing one-hundredth and lower fractions of the standard dose. Immunogenicity similarly persisted 8-10 years following both fractional and standard dose vaccination. Minor adverse events following vaccination did not differ across doses, and no serious adverse events were reported in any study arm.

CONCLUSIONS

These findings support the use of fractional dosing as a strategy for mitigating vaccine shortages. The strategy should be specifically considered for individuals who are young, immuno-competent and well nourished.