# Immune phenotyping of human immune responses to dengue vaccination and challenge

> **NIH NIH U19** · ICAHN SCHOOL OF MEDICINE AT MOUNT SINAI · 2024 · $135,718

## Abstract

PROJECT 3: PROJECT SUMMARY
Dengue virus (DENV) is the most prevalent mosquito–borne virus infecting humans in tropical and subtropical
areas of the world. There are 4 DENV serotypes, namely DENV1, DENV2, DENV3 and DENV4 circulating in
humans. Understanding the immunoprotective and immunopathogenic responses to dengue vaccines and
responses to dengue virus (DENV) infection are critical to the development of a safe and effective dengue
vaccine. To assess the innate and adaptive immune responses contributing to homo- and heterotypic immune
responses to dengue vaccination and infection, we will analyze samples obtained from two clinical trials which
evaluated the live attenuated dengue vaccine TV003 (LATV) or a trivalent admixture missing the DENV-2
component of TV003 (CIR287 and CIR300 respectively), against DENV-2 challenge. TV003 induced 100%
protection against viremia and rash following DENV-2 challenge, the trivalent formulation induced only 20%
protection against DENV-2 viremia. Using available samples from vaccine trials described above that are fully
characterized serologically, we will analyze the cellular immune responses in PBMCs generated in those
individuals over time, provided by the clinical core (Core B). With multiparametric immunological and genetic
approaches performed by the immune phenotyping core (Core C) and genetic core (Core D), we will profile
the innate and adaptive immune responses to tetra- and trivalent vaccine formulations (Aim 1) and to
challenge with rDEN230, a live attenuated DENV-2 discarded as vaccine component (Aim 2). Additionally,
we will use human tonsillar histocultures (HC) provided by core B to analyze the immune responses induced
by different admixtures of the dengue vaccines (Aim 3). Tonsils have a well-defined spatial architecture and
cellular microenvironments and can be readily dissociated for single cell assays. They also show important
features to understand the generation of innate and adaptive immune responses, like the formation of germinal
centers. These facts make them ideal for comparing cell suspension profiling assays such as Aurora flow
cytometry with tissue imaging approaches like spatial transcriptomics (Core D). The understanding of the
elements in the different vaccine formulations that confer immunogenicity and the contribution of the different
serotypes to vaccine efficacy will be crucial for the development of efficacious vaccines. Our approach will
provide important information on the generation of immune responses to vaccination and infections and the
immune signatures induced by protective vaccines versus less protective ones as determined by the data
management and analysis core (Core E). The analyses of the different cell populations present in PBMCs and
in the tonsil HC will expand our knowledge on generation of innate and adaptive immune responses and will
allow for the visualization of germinal center formation and other features important for the generation of
protective immu...

## Key facts

- **NIH application ID:** 10783787
- **Project number:** 5U19AI168631-03
- **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:** 2024
- **Award amount:** $135,718
- **Award type:** 5
- **Project period:** 2022-03-22 → 2027-02-28

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10783787

## Citation

> US National Institutes of Health, RePORTER application 10783787, Immune phenotyping of human immune responses to dengue vaccination and challenge (5U19AI168631-03). Retrieved via AI Analytics 2026-05-24 from https://api.ai-analytics.org/grant/nih/10783787. Licensed CC0.

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