Dataset Information

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.

SUBMITTER: Kareko BW

PROVIDER: S-EPMC7289542 | biostudies-literature |

REPOSITORIES: biostudies-literature

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Project description:IntroductionPrompted by recent amendments of Yellow Fever (YF) vaccination guidelines from boost to single vaccination strategy and the paucity of clinical data to support this adjustment, we used the profile of the YF-specific CD8+ T-cell subset profiles after primary vaccination and neutralizing antibodies as a proxy for potentially longer lasting immunity.Methods and findingsPBMCs and serum were collected in six individuals on days 0, 3, 5, 12, 28 and 180, and in 99 individuals >10 years after YF-vaccination. Phenotypic characteristics of YF- tetramer+ CD8+ T-cells were determined using class I tetramers. Antibody responses were measured using a standardized plaque reduction neutralization test (PRNT). Also, characteristics of YF-tetramer positive CD8+ T-cells were compared between individuals who had received a primary- and a booster vaccination. YF-tetramer+ CD8+ T-cells were detectable on day 12 (median tetramer+ cells as percentage of CD8+ T-cells 0.2%, range 0.07-3.1%). On day 180, these cells were still present (median 0.06%, range 0.02-0.78%). The phenotype of YF-tetramer positive CD8+ T-cells shifted from acute phase effector cells on day 12, to late differentiated or effector memory phenotype (CD45RA-/+CD27-) on day 28. Two subsets of YF-tetramer positive T-cells (CD45RA+CD27- and CD45RA+CD27+) persisted until day 180. Within all phenotypic subsets, the T-bet: Eomes ratio tended to be high on day 28 after vaccination and shifted towards predominant Eomes expression on day 180 (median 6.0 (day 28) vs. 2.2 (day 180) p = 0.0625), suggestive of imprinting compatible with long-lived memory properties. YF-tetramer positive CD8+ T-cells were detectable up to 18 years post vaccination, YF-specific antibodies were detectable up to 40 years after single vaccination. Booster vaccination did not increase titers of YF-specific antibodies (mean 12.5 vs. 13.1, p = 0.583), nor induce frequencies or alter phenotypes of YF-tetramer+ CD8+ T-cells.ConclusionThe presence of a functionally competent YF-specific memory T-cell pool 18 years and sufficient titers of neutralizing antibodies 35-40 years after first vaccination suggest that single vaccination may be sufficient to provide long-term immunity.

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