# Dengue Human Immunology Project Consortium (DHIPC)

> **NIH NIH U19** · ICAHN SCHOOL OF MEDICINE AT MOUNT SINAI · 2020 · $3,000,000

## Abstract

The Dengue Human Immunology Project Consortium (DHIPC) aims to identify mechanisms underlying
the human immune response to infection by or vaccination against dengue and related arboviral
diseases. It has specific goals, objectives, and critical milestones and an organizational structure that
supports this comprehensive program, and the ‘omics’ Cores are integrated with the Projects to (Figure 1).
Further, we expect to identify immune signatures that can be used as predictors or indicators of
protection or disease severity. Because the field is not static, the Cores and Projects has the flexibility to
allow for capacity building to assess new approaches that address other aspects of human immunity
through discovery research or other emerging infectious diseases (for example, the chikungunya and Zika
epidemics that occurred during the first years of this project) and have been proposed for pilot studies
(through the use of the HIPC Infrastructure and Opportunity Funds (IOF) or other funding sources). We are
using a holistic approach to address the following specific aims:
Aim 1. Measure the dynamic changes in human immune profiles following DENV infection that
correlate with outcome and the generation of immune responses in humans. This aim focuses on
characterizing immune signatures associated with infection outcomes and disease severity in natural
DENV infections, stratified by primary vs. secondary DENV infection and DENV serotype. In addition, we
will investigate how innate immune profiles influence humoral and cell-mediated adaptive immunity
following viral infection. Integration of phenotype data with data collected using different genome-wide
platforms will identify key genes and networks involved in host immunity and disease pathogenesis
(Project 1 and Cores B, C, D, E & F).
Aim 2. Compare the immune profiles in vaccinated people to people with naturally acquired DENV
infections and identify the immune signatures that correlate with DENV vaccine efficacy. Here, we
will analyze and integrate the global responses in humans vaccinated with DENV2 vaccine candidates as
well as those who are then enrolled in human challenge studies (Project 2 and Cores B, C, D, E & F).
Aim 3. Validate the immune signatures defined by the network models that predict DENV immunity
and pathogenesis. Lastly, we will perform targeted experiments focusing on selected genes and proteins
to assess the phenotypic impact on virus
replication, immune responses and host
signatures correlating with disease. Here
we will use primary human systems, such
as peripheral blood mononuclear cells
(PBMCs) and dendritic cells (DCs) that
will be infected ex vivo with the selected
Nicaraguan DENV primary isolates and
DENV vaccine candidates. We will
undertake targeted studies in those
primary cells that ablate key host genes
using siRNA and assess their impact on
the transcriptome, epigenome, and
proteome in cells deconvoluted across cell
types ex vivo (Project 3 and Cores B, C,
D, E & ...

## Key facts

- **NIH application ID:** 10056684
- **Project number:** 4U19AI118610-06
- **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:** 2020
- **Award amount:** $3,000,000
- **Award type:** 4C
- **Project period:** 2020-06-01 → 2022-05-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10056684

## Citation

> US National Institutes of Health, RePORTER application 10056684, Dengue Human Immunology Project Consortium (DHIPC) (4U19AI118610-06). Retrieved via AI Analytics 2026-05-24 from https://api.ai-analytics.org/grant/nih/10056684. Licensed CC0.

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