# Long Term Immunity Following Yellow Fever Vaccination

> **NIH NIH R01** · OREGON HEALTH & SCIENCE UNIVERSITY · 2021 · $525,681

## Abstract

PROJECT SUMMARY
Yellow fever virus (YFV) is the prototype flavivirus and is historically the most important arthropod-borne viral
pathogen of humans worldwide with ~200,000 infections annually and a mortality of ~50% in those who develop
severe symptoms. YFV is endemic throughout Africa and South America and had been largely controlled through
mass vaccination. The YFV vaccine 17D is considered one of the most effective live-attenuated virus (LAV)
vaccines ever developed. Even so, every 10-year boosts have been recommended to maintain immunity.
However, falling vaccination rates have led to a dramatic resurgence of disease in both Africa and South
America, and subsequent vaccination campaigns have depleted the global supply of 17D. In response to these
vaccine shortages, the WHO and CDC revised the 10-year boost to a once-in-a-lifetime vaccination
recommendation, despite limited supporting data: although serosurveys find that ~90% of vaccinees have
detectable neutralizing antibodies to YFV, careful review of these surveys finds that among individuals living in
YFV non-endemic settings, at least 20% of YFV vaccinees lack detectable neutralizing antibodies at >10 years
post-vaccination. While this finding must be critically evaluated in the context of ongoing outbreaks and vaccine
shortages, it also represents a unique opportunity to study how 17D induces and maintains neutralizing
antibodies in some vaccinees but not in others. Our central premise is that long-term YFV immunity is established
by host immune activation in response to vaccine viremia at the time of vaccination: downstream effects of
detectable differences in duration and magnitude of vaccine viremia at vaccination determine whether or not a
vaccinee develops life-long immunity. We propose to evaluate this premise and its broader implications in three
separate Aims: Aim 1 tests the hypothesis that vaccine viremia correlates with the long-term durability of of YFV
neutralizing antibodies. We will enroll YFV pre-vaccinees and prospectively characterize acute vaccine viremia,
acute innate immune and adaptive immune responses, and neutralizing antibody titers up to 5 years thereafter.
Aim 2 tests the hypothesis that at least 20% of 17D vaccinated subjects will lose YFV immunity between 3- and
7-years post vaccination. We will recruit and prospectively follow a cohort of 17D vaccinees vaccinated 2-3 years
prior to enrollment, comparing changes in YFV neutralizing antibodies and other immune markers over time and
characterizing individual and cohort antibody decay kinetics. In Aim 3 we use 17D revaccination as a live-virus
challenge to test the hypothesis that neutralizing antibody titers correlate with YFV protection. We will
prospectively characterize pre-boost antibodies titers, vaccine viremia, acute immune responses and post-boost
titers in vaccinees receiving boost 17D vaccinations. We expect to identify neutralizing antibody titers above
which sterilizing immunity is conferred and t...

## Key facts

- **NIH application ID:** 10098296
- **Project number:** 5R01AI145835-02
- **Recipient organization:** OREGON HEALTH & SCIENCE UNIVERSITY
- **Principal Investigator:** William Messer
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2021
- **Award amount:** $525,681
- **Award type:** 5
- **Project period:** 2020-02-05 → 2025-01-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10098296

## Citation

> US National Institutes of Health, RePORTER application 10098296, Long Term Immunity Following Yellow Fever Vaccination (5R01AI145835-02). Retrieved via AI Analytics 2026-05-22 from https://api.ai-analytics.org/grant/nih/10098296. Licensed CC0.

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