# Human neutralizing antibodies for Zika virus

> **NIH NIH R01** · VANDERBILT UNIVERSITY MEDICAL CENTER · 2020 · $649,057

## Abstract

Zika virus (ZIKV) is an emerging mosquito-transmitted flavivirus that has become a global public
health threat. The World Health Organization declared ZIKV and its suspected link to birth defects
an international public health emergency on February 1, 2016. Epidemics of ZIKV infection have
been reported in Mexico, and Central and South America and linked to cases of Guillain-Barre
syndrome in adults and microcephaly in newborn infants in the setting of maternal infection during
pregnancy. Despite the potential for infecting and causing disease in millions, specific diagnostics,
treatments, or vaccines for ZIKV are not available. The primary goal of this collaborative and
interactive project is to define the molecular, genetic, immunologic, characteristics of newly-
isolated neutralizing human mAbs with broad specificity against all strains of ZIKV. A second goal
is to define the mechanistic correlates of protection by neutralizing mAbs. A third goal is to
determine whether cross-reactive anti-DENV human mAbs that bind to ZIKV are
protective/therapeutic or pathogenic in a newly developed mouse model of ZIKV. We hypothesize
that potently inhibitory mAbs recognize epitopes associated with key ZIKV structural transitions
with high affinity and block one or more keys step during entry (e.g., attachment, entry, or fusion).
Our approach will include high-efficiency isolation of human mAbs and with detailed functional
and structural analyses to define how and why human mAbs inhibit ZIKV. We also will explore
the significance of Fc?R binding and determine whether ZIKV is similar or different than DENV in
the context of antibody-mediated immune enhancement of disease. In addition to fundamental
studies of ZIKV pathogenesis and immunity, these studies also will result in the generation of a
group of fully human mAbs that can be tested in preclinical models and could be developed rapidly
as therapeutic or prophylactic biologic drugs for humans. Studies in this project also will inform
ongoing diagnostic and future vaccine efforts against ZIKV, as they will define the principal major
antigenic sites epitopes associated with potent type-specific antibody-mediated virus
neutralization and protection. The collaborative multidisciplinary group assembled to conduct
studies in this multi-PI application already collaborates productively, with a strong track record in
studies of dengue, chikungunya and other arthropod-borne viruses, and has a clear division of
labor for the studies proposed in this application.

## Key facts

- **NIH application ID:** 9843443
- **Project number:** 5R01AI127828-04
- **Recipient organization:** VANDERBILT UNIVERSITY MEDICAL CENTER
- **Principal Investigator:** James E Crowe
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $649,057
- **Award type:** 5
- **Project period:** 2017-01-01 → 2021-12-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/9843443

## Citation

> US National Institutes of Health, RePORTER application 9843443, Human neutralizing antibodies for Zika virus (5R01AI127828-04). Retrieved via AI Analytics 2026-05-22 from https://api.ai-analytics.org/grant/nih/9843443. Licensed CC0.

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