# Previous exposure to dengue as a risk factor for Zika during pregnancy

> **NIH NIH R01** · UNIVERSITY OF MINNESOTA · 2020 · $630,599

## Abstract

Project Summary
Dengue virus (DENV) is endemic in many regions of the Americas where Zika virus (ZIKV) is emerging. These
two viruses are closely related genetically and antigenically, so immunity to DENV may influence the outcome
of ZIKV infection. The goal of this project is to understand the impact of pre-existing DENV immunity induced
by infection or vaccination on ZIKV infection during pregnancy. This question is important because it has been
hypothesized that the unexpectedly high rate of adverse consequences associated with ZIKV infection during
pregnancy may be the result of previous infection with one of the four DENV serotypes. Primary infection with
one DENV serotype is protective against secondary infection with the same serotype. Secondary infection
with a different serotype can lead to enhanced disease because cross-reactive, inadequately neutralizing, an-
tibodies can facilitate enhanced viral replication and skewed immune responses. DENV and ZIKV are similar
enough in the envelope protein (the major target of these enhancing antibodies) that ZIKV could theoretically
function as a “fifth” DENV serotype. This has been explored to some degree, but controversy remains, as
some groups have reported cross-protection while others have reported the potential for enhanced disease.
Critically, interactions between DENV and ZIKV have not been explored in the setting of pregnancy,
even though congenital ZIKV infection is associated with birth defects. Accordingly, through this NIH/
NIAD R01 we will use our nonhuman primate model of ZIKV infection to evaluate whether the severity of ma-
ternal and fetal ZIKV infection during pregnancy are enhanced by previous exposure to DENV. There are two
Specific Aims:
Specific Aim 1. Define the impact of prior DENV infection on the severity of maternal and neonatal
ZIKV infection in pregnant macaques.
Specific Aim 2. Define the impact of prior DENV vaccination on the severity of maternal and neonatal
ZIKV infection in pregnant macaques.
In these studies, we will contrast maternal viremia, immune responses, and fetal outcomes with those in
DENV-naive individuals infected identically with ZIKV. Our strategy to induce DENV-specific immune re-
sponses includes exposure to both wildtype DENV and a leading DENV vaccine candidate, Sanofi Pasteur’s
Dengvaxia®. These studies are critically important because 1) ZIKV is circulating in many locations where
DENV is hyperendemic and 2) Dengvaxia® is currently licensed for use, and licensure of other DENV vaccines
is imminent, in areas where ZIKV is circulating. By definition, large-scale vaccination campaigns will increase
the prevalence of DENV immunity. Whether immunization with Dengvaxia®—which simultaneously exposes
an individual to all four DENV serotypes—can lead to more severe ZIKV disease is unknown. The results from
these experiments will provide important answers to an epidemiologically relevant question; is it safe to vacci-
nate against dengue where ZIKV als...

## Key facts

- **NIH application ID:** 9840868
- **Project number:** 5R01AI132563-04
- **Recipient organization:** UNIVERSITY OF MINNESOTA
- **Principal Investigator:** Matthew T Aliota
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $630,599
- **Award type:** 5
- **Project period:** 2018-01-01 → 2022-12-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/9840868

## Citation

> US National Institutes of Health, RePORTER application 9840868, Previous exposure to dengue as a risk factor for Zika during pregnancy (5R01AI132563-04). Retrieved via AI Analytics 2026-05-24 from https://api.ai-analytics.org/grant/nih/9840868. Licensed CC0.

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