# Epitope-focused vaccine strategies against Zika virus

> **NIH NIH P01** · ROCKEFELLER UNIVERSITY · 2020 · $1,347,756

## Abstract

Summary - Overall (PI: Michel Nussenzweig)
Although Zika virus (ZIKV) infection typically leads to a mild disease, it produces grim consequences when it
occurs during pregnancy. Vertical transmission can lead to fetal demise, microcephaly or other developmental
aberrations in up to nearly half of the cases. ZIKV is a global challenge; according to the CDC, nearly 40% of
the world population lives in regions inhabited by the mosquito vectors that are competent for ZIKV. Therefore,
a vaccine is needed that is both safe and efficacious in preventing ZIKV infection.
 ZIKV is a flavivirus like dengue (DENV), which is responsible for severe human disease and mortality.
There are 4 serotypes of DENV (DENV1-4) that are antigenically very similar to each other and to ZIKV. This
similarity can confer cross-protection, but it may also be responsible for causing a severe hemorrhagic form of
dengue when antibodies elicited in response to one of the serotypes are cross-reactive and non- or poorly
neutralizing to another serotype. The cross-reactive antibodies are thought to form immune complexes that
enhance the infection and the disease, a phenomenon that is referred to as Antibody Dependent Enhancement
(ADE). In vitro and in vivo experiments support the view that the ADE extends to ZIKV. Thus, a desirable goal
is to develop a ZIKV vaccine that selectively elicits antibodies to neutralizing epitopes of ZIKV, while at the
same time avoiding those to other flaviviruses, including DENV, that are non-neutralizing and potentially
enhancing. Doing so requires an understanding of the neutralizing antibody response to ZIKV and structural
understanding of how these antibodies recognize ZIKV surface proteins.
 This Program Project builds upon an established collaboration between the Nussenzweig, Bjorkman, and
Rice laboratories. Its ultimate goal is to discover and characterize a panel of neutralizing epitopes on the ZIKV
surface, and to use this information to design and test candidate vaccines to elicit antibodies that selectively
target such neutralizing epitopes. We propose two highly interrelated projects led by Drs. Michel
Nussenzweig and Pamela Bjorkman, which will be supported by a Scientific Core led by Dr. Charles Rice,
who will provide the expertise in virology. In Project 1, previously characterized samples from exceptional
ZIKV responders will be used for neutralizing antibody discovery from memory B cells. Project 2 will
characterize the antibodies and their epitopes structurally, and the information obtained will enable the rational
design and production of candidate immunogens. The immunogens designed in Project 2 will be evaluated in
Project 1 using wild type and genetically humanized mice for safety and efficacy in protection against ZIKV
and DENV infection. Activities in both projects will be supported by the Virology and Administrative Cores.
The proposed experiments aim at developing vaccine candidates for subsequent evaluation in non-human
primates...

## Key facts

- **NIH application ID:** 9982200
- **Project number:** 5P01AI138938-03
- **Recipient organization:** ROCKEFELLER UNIVERSITY
- **Principal Investigator:** Michel C Nussenzweig
- **Activity code:** P01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $1,347,756
- **Award type:** 5
- **Project period:** 2018-08-01 → 2023-07-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/9982200

## Citation

> US National Institutes of Health, RePORTER application 9982200, Epitope-focused vaccine strategies against Zika virus (5P01AI138938-03). Retrieved via AI Analytics 2026-05-22 from https://api.ai-analytics.org/grant/nih/9982200. Licensed CC0.

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