# Flavivirus Infections: Pathogenesis and Prevention

> **NIH NIH P01** · UNIVERSITY OF RHODE ISLAND · 2020 · $1,892,293

## Abstract

Project Summary/Abstract
 The overall objective of this Program Project is to define individual- and population-level
immunological benchmarks for the prevention of dengue virus (DENV) infection and disease. Prevention
of dengue is a high priority for the NIH and other organizations given its increasing medical and
economic impact in both developing and developed countries. Dengue vaccine development has seen
major progress, but encouraging results from efficacy trials have been offset by suboptimal efficacy and
an increased risk for hospitalized dengue in some subpopulations. These results reinforce the need for
research to fill gaps in current understanding of the determinants of the outcome of DENV infection.
Critical elements for such research include capturing clinically-relevant endpoints, analyzing both natural
infection and vaccination, and considering the epidemiologic context of infection. This program
addresses this objective through synergistic epidemiologic, clinical, virologic, and immunologic
investigations. Project 1 (Kamphaeng Phet Family Cohort Study) will extend surveillance of a household-
based cohort of >3,000 individuals across the age spectrum to define correlates of risk over the course of
sequential DENV exposures. Project 2 (Correlates of Protection and Risk in Dengue Transmission
Clusters) will apply geographic cluster investigations to study correlates of risk in proximity to exposure
and during the early phase of infection. Project 3 (Immunologic Determinants of Outcome in Dengue
Virus Infection and Vaccination) will extend surveillance of a cohort of participants in a phase III dengue
vaccine trial to analyze the evolution of immunological memory over time and its associations with
outcome. The Administrative Core, Data Management and Statistics Core, and the Clinical Research
Laboratory Core will provide essential scientific and fiscal oversight, coordinate data management and
analysis, and provide laboratory infrastructure for specimen processing and testing, respectively, in
support of all three Projects. As a whole, this program will: a) define immune responses to DENV at the
individual level that are associated with the risk of infection and/or disease, capturing the full spectrum of
previous DENV exposure, b) define immune responses that are associated with the risk of infection
and/or disease after immunization with the licensed dengue vaccine, c) define immune responses at the
population level that are associated with the risk of infection and/or disease in individual subjects, and d)
determine the contribution of waning immunity after natural infection or vaccination to the risk of infection
and/or disease. The program builds on concepts, techniques, and expertise established during previous
periods, and its findings should have basic science as well as clinical and public health implications.

## Key facts

- **NIH application ID:** 9980762
- **Project number:** 5P01AI034533-28
- **Recipient organization:** UNIVERSITY OF RHODE ISLAND
- **Principal Investigator:** Alan L Rothman
- **Activity code:** P01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $1,892,293
- **Award type:** 5
- **Project period:** 1997-01-01 → 2023-07-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/9980762

## Citation

> US National Institutes of Health, RePORTER application 9980762, Flavivirus Infections: Pathogenesis and Prevention (5P01AI034533-28). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/9980762. Licensed CC0.

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