# PROJECT 2: Linking Vaccine-Induced Antibody Responses to Protective or Disease Enhancing Immunity

> **NIH NIH P01** · UNIVERSITY OF CALIFORNIA BERKELEY · 2021 · $407,000

## Abstract

PROJECT 2: Linking Vaccine Induced Antibody Responses to Protective or Disease Enhancing Immunity
(University of North Carolina, Chapel Hill).
SUMMARY
Vaccination is the most promising and cost-effective strategy for controlling the global pandemic caused by the
four dengue virus (DENV) serotypes. DENV vaccines based on tetravalent live attenuated (TV-DLAV)
formulations are at different stages of clinical development. Recently, DENV vaccines have faced major
setbacks in clinical studies, such as poorly balanced immune responses across the four DENV serotypes,
variable vaccine efficacy depending on the baseline immune status of children, vaccine responses that are more
effective against strains that closely match the vaccine strain and, most significantly, vaccine-primed severe
dengue disease upon exposure to wild-type DENVs. It has been challenging to understand and solve these
problems because we still lack robust immune correlates that predict DENV vaccine efficacy and safety. The
overall approach of Project 2 is to characterize antibody (Ab) responses in people who receive TV-DLAV. To link
vaccine-induced Ab responses to specific outcomes such as protection, vaccine failure and vaccine-primed
severe disease, our studies utilize samples from vaccinated people with known outcomes upon exposure to wild-
type DENVs. We will test the hypothesis that in people with no prior immunity to DENVs who are vaccinated,
durable protection will require the induction of Abs to type-specific (TS) tertiary and quaternary structure epitopes
on each DENV serotype (Specific Aim 1.1). In children who are seronegative at baseline, we will test if low-
avidity cross-reactive (XR) Abs induced by vaccination increase the risk of severe dengue disease (Specific
Aim 1.2). In people with pre-existing immunity to DENV, we will explore if vaccine efficacy is linked to the
activation of DENV-specific memory B cells and the induction of cross-protective Ab responses, similar to
protective responses in natural 2° DENV infections (Specific Aim 2). We will also conduct studies to define the
impact of genotypic variation within each DENV serotype on vaccine efficacy (Specific Aim 3). This project will
define immune correlates and mechanisms of vaccine efficacy and safety in people with different levels of
baseline immunity to DENV. Project 2 is highly synergistic with the other Projects and Cores in this P01. We
will generate reagents (chimeric epitope transplant flaviviruses and recombinant antigens) for use by other
Projects (Projects 1 & 4), share clinical samples (Core C, Projects 1 & 3), compare Ab responses to vaccines
and natural DENV infections (Projects 1 and 4) and integrate the analysis (Core B) of the Ab and T cell response
to DENV vaccines (Project 3).

## Key facts

- **NIH application ID:** 10244877
- **Project number:** 5P01AI106695-07
- **Recipient organization:** UNIVERSITY OF CALIFORNIA BERKELEY
- **Principal Investigator:** Aravinda M. DeSilva
- **Activity code:** P01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2021
- **Award amount:** $407,000
- **Award type:** 5
- **Project period:** 2015-07-29 → 2025-07-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10244877

## Citation

> US National Institutes of Health, RePORTER application 10244877, PROJECT 2: Linking Vaccine-Induced Antibody Responses to Protective or Disease Enhancing Immunity (5P01AI106695-07). Retrieved via AI Analytics 2026-05-22 from https://api.ai-analytics.org/grant/nih/10244877. Licensed CC0.

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