# Dengue-Zika: Correlates of Cross-Protection in Non-Human Primates

> **NIH NIH R01** · UNIVERSITY OF PUERTO RICO MED SCIENCES · 2020 · $714,650

## Abstract

Abstract
Zika virus (ZIKV) is a re-emerging mosquito-borne Flavivirus that recently caused an outbreak in the Americas. The
establishment of ZIKV transmission cycle in tropical/sub-tropical regions that are endemic to other close-related flaviviruses
such as Dengue virus (DENV) has raised concerns, mainly by their cross-immunological interactions and the implications
of this for development of severe clinical manifestations. Several groups have demonstrated that DENV-immune serum
from humans can enhance ZIKV infection in vitro and in vivo in an immunodeficient mice model. This phenomenon known
as Antibody Dependent-Enhancement (ADE) has been linked to severe dengue clinical manifestations. Little is known about
the effect of a previous immunity to ZIKV on a subsequent DENV infection. It is highly necessary to characterize correlates
of protection in the control of a heterologous secondary DENV or ZIKV infection in the presence of previous DENV or
ZIKV immunity in an immunological competent animal model that resemble the human immune system like the Non-
Human Primates. Our group have preliminary data showing a potential protective role of the cellular immune response in
dengue- immune or ZIKV-immune subjects during a heterologous secondary infection with ZIKV or dengue. The overall
hypothesis behind this work is that the cross-primed cellular immune response may be critical controlling the DENV and
ZIKV infection and provides heterologous protection against each other. To test this hypothesis, we propose a series of
straightforward experiments by depleting the CD4+ or CD8+ or CD20+ cells at different time points before a primary or a
secondary infection with dengue or ZIKV. This type of experiment has not been performed before in NHP. For these
experiments we will use rhesus macaques bred and housed at the Caribbean Primate Research Center that has proven to be
the purer Indian-origin macaque population of all populations in the USA or imported animals, without having a significant
level of inbreeding. For first time in any study in the flavivirus field, we will use a large data on the MHC typing of this
population to characterize specific CD4 and/or CD8 T cells epitopes playing a role in the T cells immune response against
dengue and ZIKV. Understanding correlates of protection between ZIKV and DENV is essential to anticipate the outcome
of the secondary infection, the design of diagnostics methods and more relevant, to support the design of highly effective
ZIKV and DENV vaccines in the scenario of previous DENV or ZIKV immunity, respectively. Undoubtedly, NHP provide
us with a unique immunological tool very close to the human system to provide the answers to the questions we are outlying
on this application.

## Key facts

- **NIH application ID:** 9862437
- **Project number:** 1R01AI148264-01
- **Recipient organization:** UNIVERSITY OF PUERTO RICO MED SCIENCES
- **Principal Investigator:** CARLOS A SARIOL
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $714,650
- **Award type:** 1
- **Project period:** 2020-01-09 → 2024-12-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/9862437

## Citation

> US National Institutes of Health, RePORTER application 9862437, Dengue-Zika: Correlates of Cross-Protection in Non-Human Primates (1R01AI148264-01). Retrieved via AI Analytics 2026-05-22 from https://api.ai-analytics.org/grant/nih/9862437. Licensed CC0.

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