Persistence of Neutralizing Antibody Responses Among Yellow Fever Virus 17D Vaccinees Living in a Nonendemic Setting

Abstract

Background: The once-in-a-lifetime recommendation for vaccination against yellow fever virus (YFV) has been controversial, leading to increased scrutiny of the durability of immunity after 17D vaccination.

Methods: This is a cross-sectional analysis of 17D vaccinees living in nonendemic Portland, Oregon. Neutralization assays were used to determine YFV immunity. The relationships between 17D immunity and vaccination history, demographics, and travel were evaluated using nominal logistic regression.

Results: Seventy-one of 92 (77.2%) subjects were YFV seropositive (90 percent plaque reduction neutralization test ≥1:10) at all timepoints, and 24 of 38 (63.8%) were YFV seropositive at ≥10 years after single-dose vaccination. No relationship was found between YFV immunity and time in endemic countries, other flavivirus immunity, or demographics. Subjects were most likely to become seronegative between 3 and 12 years postvaccination (logistic regression, odds ratio [OR] = 1.75; 95% confidence interval [CI], 1.12-2.73). A comparison of our results and 4 previous studies of YFV nonendemic vaccinees found that overall, 79% (95% CI, 70%-86%) of vaccinees are likely to be seropositive ≥10 years postvaccination.

Conclusions: These results suggest that 1 in 5 17D vaccinees will lack neutralizing antibodies at ~10 years postvaccination, and a booster vaccination should be considered for nonendemic vaccinees before travel to regions where there is a high risk of YFV transmission.

Keywords: 17D; immunity; neutralizing antibodies; vaccine.

Figure 1.

Plot of 90 percent plaque reduction neutralization test (PRNT₉₀) vs years postvaccination. The PRNT₉₀ values are fold serum dilution. Horizontal black line is at PRNT₉₀ = 1:10, the limit of detection for our assay. Vertical dotted line indicates the median of the distribution of subjects by year postvaccination, 8.5 years. Curved line shows estimated power (log-log) regression curve of PRNT₉₀ vs years postvaccination: y = Exp (4.48 − 0.351 × log(years postvaccination)); P = .0062.

Figure 2.

Forest plot of point a random effects model estimate of proportion seropositive and 95% confidence intervals (CIs) for the 5 nonendemic studies in Supplemental Table 1. Events are the number of positive cases in each study. Point estimates for each study are shown as squares and whiskers show 95% CIs. The summary random effects model point estimate and 95% CIs are shown as a diamond. Heterogeneity, τ ², χ ², and P value for the Q statistic are shown below. Estimates of heterogeneity were calculated by first invoking the random effects model with double-arcsine transformation and the restricted maximum likelihood estimator method.