# Project 3 - Ex vivo immune profiling of dengue viruses and vaccines

> **NIH NIH U19** · ICAHN SCHOOL OF MEDICINE AT MOUNT SINAI · 2021 · $299,999

## Abstract

Dengue is the most prevalent mosquito-borne viral disease causing disease in humans. Dengue disease may 
present as a non-specific febrile illness, dengue fever (DF), or as a more severe infection marked by 
hemorrhage or circulatory failure or shock, dengue hemorrhagic fever (DHF) or dengue shock syndrome (DSS). 
There are currently no licensed vaccines or therapeutics for dengue virus (DENV). Our laboratory has 
optimized and utilized human ex vivo models for virus infections, which have been very useful for elucidating 
mechanisms of innate immune evasion by DENV in specific cell types. Understanding virus-host interactions 
during DENV infections and the molecular mechanisms involved in the generation of immune responses is one 
of the crucial factors that will lead to the development of effective and safe vaccines and therapeutics. 
This project will analyze immune responses to DENV infections ex vivo using two robust systems of human 
PBMCs and DCs, which are targets for DENV infection in humans. This controlled system of DENV infection 
captures early events of the virus-host interaction. We will profile innate immune responses to DENV primary 
isolates circulating in Nicaragua (Project 1) and DENV vaccine strains (Takeda Vaccines Inc., Project 2). 
Selected strains will be then used for the in depth characterization of the innate immune response, cellular 
transcriptome, epigenome and proteome in collaboration with the Genomics (Core B), Proteomics (Core C) 
and immune monitoring Core (Core D) in PBMCs or DCs upon viral exposure. We will identify host proteins 
that differentially mediate innate immune responses and impact viral replication with the same DENV isolates 
and vaccines strains by siRNA screens in DCs. Data will be managed and analyzed by the Data Analysis and 
Modeling Core (Core E) and the Data Management and Dissemination Core (Core F) to define parameters and 
build cellular and molecular networks important for innate immunity to DENV. Networks will be subsequently 
integrated with those generated from in vivo studies in Projects 1 (natural infections) and 2 (vaccine trials). 
Also, our ex vivo systems will serve to identify sets of genes through global analysis to design targeted assays 
for in vivo studies in Projects 1 and 2 and to validate the role of specific genes important for innate immunity to 
DENV infection identified in vivo.

## Key facts

- **NIH application ID:** 10153665
- **Project number:** 5U19AI118610-07
- **Recipient organization:** ICAHN SCHOOL OF MEDICINE AT MOUNT SINAI
- **Principal Investigator:** Ana Fernandez-Sesma
- **Activity code:** U19 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2021
- **Award amount:** $299,999
- **Award type:** 5
- **Project period:** 2020-06-01 → 2023-01-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10153665

## Citation

> US National Institutes of Health, RePORTER application 10153665, Project 3 - Ex vivo immune profiling of dengue viruses and vaccines (5U19AI118610-07). Retrieved via AI Analytics 2026-05-24 from https://api.ai-analytics.org/grant/nih/10153665. Licensed CC0.

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