# Project 3:  Immunologic Determinants of Outcome in Dengue Virus Infection and Vaccination

> **NIH NIH P01** · UNIVERSITY OF RHODE ISLAND · 2021 · $511,266

## Abstract

Project Summary/Abstract
 The overall objective of Project 3 is to identify the elements of immunological memory induced by
natural DENV infection and vaccination that correlate with outcome upon subsequent DENV exposure.
Immunological memory is important to vaccine efficacy. Many DENV infections occur in the context of
pre-existing immunological memory, and the consequences can be either beneficial (reduced risk of
infection and/or disease) or pathological (increased risk of infection and/or disease); defining the
characteristics that distinguish these outcomes will advance dengue vaccine development and
implementation. Previous studies by our group have begun to identify associations between
immunological memory and clinical outcomes of DENV infection. The proposed studies will address gaps
in knowledge regarding the mechanisms of these associations and the kinetics of DENV-specific
immunological memory. We hypothesize that specific populations of memory T and B lymphocytes
defined by specificity and phenotype determine the outcome of infection, and that changes over time in
populations of memory lymphocytes correlate with the time-varying risk of DENV infection and disease.
These hypotheses will be tested using blood samples from Thai cohort studies as well as extended
observation of a unique cohort of participants in the phase III trial of the chimeric yellow fever-dengue
vaccine in Cebu, the Philippines, who have had annual blood collections and active surveillance for
acute dengue illnesses for ~5 years. The Specific Aims to be addressed in Project 3 are to: 1) define the
memory T and B cell populations in pre-infection blood samples that are associated with the outcome of
subsequent DENV infection; 2) define the changes in frequency, specificity, and function of DENV-
specific T cell and B cell populations over time after natural infection and their associations with incident
DENV infections; and 3) define the changes in frequency, specificity, and function of DENV-specific T
cell and B cell populations over time after vaccination and their associations with risk of DENV infection
and disease.
 Project 3’s focus on DENV-specific immunological memory and its correlations with clinical
outcome directly address the overall objectives of this Program Project. Assays developed in Project 3
will be extended to the study cohorts of Projects 1 and 2, and vice versa. Project 3 will utilize Core A for
project administration, Core B for data management and statistical analysis, and Core C for processing
of clinical specimens, diagnostic testing, and assays of antibody specificity and function. The results of
these studies will be useful to improve understanding of previous vaccine trial results and to guide the
evaluation of current vaccine candidates.

## Key facts

- **NIH application ID:** 10225610
- **Project number:** 5P01AI034533-29
- **Recipient organization:** UNIVERSITY OF RHODE ISLAND
- **Principal Investigator:** Alan L Rothman
- **Activity code:** P01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2021
- **Award amount:** $511,266
- **Award type:** 5
- **Project period:** 1997-01-01 → 2023-07-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10225610

## Citation

> US National Institutes of Health, RePORTER application 10225610, Project 3:  Immunologic Determinants of Outcome in Dengue Virus Infection and Vaccination (5P01AI034533-29). Retrieved via AI Analytics 2026-05-22 from https://api.ai-analytics.org/grant/nih/10225610. Licensed CC0.

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