NIFTY (250 IU)
Trial question
Is low-dose vaccine noninferior to standard-dose yellow fever vaccine in adults with no history of yellow fever vaccination or infection?
Study design
Multi-center
Double blinded
RCT
Population
Characteristics of study participants
65.0% female
35.0% male
N = 240
240 patients (157 female, 83 male).
Inclusion criteria: adults with no history of yellow fever vaccination or infection.
Key exclusion criteria: contraindications to yellow fever vaccination; corticosteroid or other immunosuppressive therapy; thymus disorder; previous yellow fever vaccination; previous yellow fever infection; pregnancy/lactation.
Interventions
N=120 low-dose vaccine (fractional dose of 250 IU yellow fever vaccine).
N=120 standard-dose vaccine (dose of 13,803 IU yellow fever vaccine).
Primary outcome
Seroconversion at day 28
94%
98%
98.0 %
73.5 %
49.0 %
24.5 %
0.0 %
Low-dose
vaccine
Standard-dose
vaccine
Difference not exceeding
non-inferiority
margin ✓
Difference not exceeding non-inferiority margin in seroconversion at day 28 (94% vs. 98%; ARD -4.4, 95% CI -9.4 to 0.7).
Secondary outcomes
Significant decrease in seroconversion at day 10 (50% vs. 85%; ARD -34.6, 95% CI -48.7 to -20.5).
Significant decrease in seroconversion at day 365 (92% vs. 99%; ARD -7.1, 95% CI -12.8 to -1.3).
Significant decrease in seroconversion at day 730 (84% vs. 96%; ARD -11.6, 95% CI -20.6 to -2.6).
Safety outcomes
No significant difference in adverse events.
Conclusion
In adults with no history of yellow fever vaccination or infection, low-dose vaccine was noninferior to standard-dose vaccine with respect to seroconversion at day 28.
Reference
Derick Kimathi, Aitana Juan-Giner, Ndeye S Bob et al. Low-Dose Yellow Fever Vaccine in Adults in Africa. N Engl J Med. 2025 Feb 20;392(8):788-797.
Open reference URL