# Immunity to dengue viruses

> **NIH NIH U19** · ROCKEFELLER UNIVERSITY · 2021 · $535,286

## Abstract

PROJECT SUMMARY
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Dengue viruses are mosquito-borne flaviviruses of immense public health impact that cause a spectrum of
disease in humans ranging from mild to fatal. Progression to severe dengue disease is promoted by the
presence of non-neutralizing anti-dengue IgGs that modulate virus and cytokine production in Fc receptor-
bearing cells. We have shown that progression to severe dengue disease is promoted by the presence of anti-
dengue antibodies with abundant afucosylated Fc glycoforms, a modification that enhances affinity of the Fc for
a specific activating Fc receptor, FcγRIIIa. Thus, our data point to a role for FcγRIIIa in the pathogenesis of
dengue disease. In this proposal we will study samples from Phase III trials of a live, attenuated tetravalent
dengue virus vaccine, CYD-TDV (Dengvaxia, Sanofi Pasteur), to define mechanism involved in human immunity
to dengue viruses. Recent analyses of data from the Phase III trials of CYD-TDV showed that risk for disease
was increased in some study cohorts by vaccination. This finding highlights the importance of understanding
how antibody responses to dengue vaccination are regulated and molecular mechanisms by which antibodies
can enhance dengue infections. Aims in this proposal will: a) define regulators of Fc fucosylation on antibodies
elicited by CYD-TDV vaccination or by natural dengue infection in humans; b) define associations between post-
vaccination/pre-infection anti-dengue antibody repertoires and susceptibility to dengue disease during a 5-year
follow-up period after vaccination; c) define mechanisms by which FcγRIIIa impacts dengue infections and
disease pathogenesis. Collectively, these aims will advance our fundamental understanding of mechanisms
regulating human immunity to dengue viruses and guide the design of safe, effective dengue virus vaccines.

## Key facts

- **NIH application ID:** 10134217
- **Project number:** 5U19AI111825-08
- **Recipient organization:** ROCKEFELLER UNIVERSITY
- **Principal Investigator:** Taia Wang
- **Activity code:** U19 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2021
- **Award amount:** $535,286
- **Award type:** 5
- **Project period:** 2014-04-01 → 2024-03-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10134217

## Citation

> US National Institutes of Health, RePORTER application 10134217, Immunity to dengue viruses (5U19AI111825-08). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/10134217. Licensed CC0.

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