# PROJECT 1: Quality of B Cell and Antibody Responses to Natural Dengue Virus Infections

> **NIH NIH P01** · UNIVERSITY OF CALIFORNIA BERKELEY · 2021 · $442,235

## Abstract

PROJECT 1: Quality of B Cell and Antibody Responses to Natural Dengue Virus Infections
(University of California, Berkeley)
SUMMARY
The four dengue virus serotypes (DENV1-4) cause the most important mosquito-borne viral disease of humans,
with ~390 million infections annually and over 3 billion people worldwide at risk of infection. Yet, no treatment is
currently approved for use in humans, and the only registered vaccine is problematic. The overall approach of
Project 1 is to take advantage of unique Nicaraguan sample sets to address complex questions about DENV
antibody and B cell immunology in a relevant clinical and epidemiological context. The Project is designed to
analyze the antibody/B cell immune profile in relation to infection outcome, disease severity, and antibody
dynamics. Each aim also addresses specific fundamental questions in dengue immunology. The overall
hypothesis of this project is that the quality of B cell and antibody responses, as detemined by the repertoire
and characteristics of the antibodies and B cells, impacts outcome of subsequent DENV infection as well as the
long-term antibody response. The focus is on characterizing the repertoire and dynamics of the antibody
response before and after primary and secondary infections in more detail as new state-of-the-art tools become
available in our P01 program. Each aim derives from findings and reagents arising from the current P01.
Importantly, we integrate classical state-of-the-art molecular genetics and systems serology approaches
to comprehensively examine both antigen-specific and Fc characteristics and effector functions that
predict protection or pathogenesis with unprecedented resolution. The proposed research is possible due
to the ongoing Pediatric Dengue Cohort Study (2004-present), a community-based prospective cohort study in
Managua, Nicaragua, following ~3,700 children, now in its 15th year, and the Dengue Hospital-based Study
(2005-present) in Managua, which together enable investigation of pre-infection samples, documented repeat
DENV infections, and long-term B cell/antibody responses. This project is highly synergistic with the other
Projects in this P01 by sharing similar samples (Projects 3 & 4) and methods and reagents (Project 2) and
integrating computational biological analyses and statistical models (Core B) of the B cell/antibody response
during DENV natural infections with the T cell response to DENV (Project 3) and with the immune response
obtained after live attenuated DENV vaccination (Project 2). Project 1 Aim 1 will define the complete repertoire
of type-specific antibodies in dengue-endemic populations in Asia and the Americas, define the footprint of major
antigenic sites, and investigate the effect of genotype on epitope recognition in polyclonal sera. Aim 2 will
determine predictors of clinical outcome in terms of antibody repertoire and Fc effector function, in relation to
inapparent vs. symptomatic infection as well as mild vs. severe ...

## Key facts

- **NIH application ID:** 10244876
- **Project number:** 5P01AI106695-07
- **Recipient organization:** UNIVERSITY OF CALIFORNIA BERKELEY
- **Principal Investigator:** Eva Harris
- **Activity code:** P01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2021
- **Award amount:** $442,235
- **Award type:** 5
- **Project period:** 2015-07-29 → 2025-07-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10244876

## Citation

> US National Institutes of Health, RePORTER application 10244876, PROJECT 1: Quality of B Cell and Antibody Responses to Natural Dengue Virus Infections (5P01AI106695-07). Retrieved via AI Analytics 2026-05-22 from https://api.ai-analytics.org/grant/nih/10244876. Licensed CC0.

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