# A novel strategy for vaccine-induced protection against maternal-to-fetal transmission of Zika virus

> **NIH NIH R01** · LA JOLLA INSTITUTE FOR IMMUNOLOGY · 2024 · $894,640

## Abstract

Project Summary
The long-term goal of this project is to develop a vaccine that confers robust and durable protection against
transplacental transmission of Zika virus (ZIKV). Accomplishing this goal may be challenging in that the vaccine
may need to induce both antibody and T cell responses to confer highly effective protection against ZIKV at the
maternal-fetal interface (MFI). Studies with pregnant women in Brazil have suggested that antibody responses
may contribute to pathogenesis of congenital Zika syndrome (CZS) and neutralizing antibody responses may
not correlate with protection against CZS. Recent human studies also suggest that the anti-ZIKV antibody
response may be less durable than T cell response. However, ongoing ZIKV vaccine development efforts are
focused on eliciting mainly antibody responses. Based on our published data demonstrating a critical role for
CD8 T cells in protecting against ZIKV infection in multiple mouse models, we will test our central hypothesis
that a robust ZIKV vaccine-induced CD8 T cell response in mothers is required to provide strong and durable
protection against transplacental transmission of ZIKV. Our replicon RNA vaccine expressing ZIKV
premembrane (prM) and envelope (E) or nonstructural protein 3 (NS3) induces robust protection against ZIKV
infection in pregnant mice but only partial protection in their fetuses. Therefore, we will use these replicon RNA
vaccines and mouse models to achieve the following Specific Aims: 1) Improve vaccine-induced protection
against ZIKV infection during pregnancy, and identify the maternal immune responses associated with the most
protective and durable vaccines. 2) Test the role of CD8 T cells in vaccine-induced protection, and determine
precise features of MFI CD8 T cells elicited by the most protective and durable vaccine. We have expertise in
examining flaviviral pathogenesis and immunity using mouse models. We also have a longstanding collaboration
with colleagues at our institute and UC San Diego to investigate virus-host interactions using genomics and
histopathology-informed approaches.

## Key facts

- **NIH application ID:** 10982417
- **Project number:** 1R01AI180196-01A1
- **Recipient organization:** LA JOLLA INSTITUTE FOR IMMUNOLOGY
- **Principal Investigator:** Sujan Shresta
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2024
- **Award amount:** $894,640
- **Award type:** 1
- **Project period:** 2024-06-07 → 2029-04-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10982417

## Citation

> US National Institutes of Health, RePORTER application 10982417, A novel strategy for vaccine-induced protection against maternal-to-fetal transmission of Zika virus (1R01AI180196-01A1). Retrieved via AI Analytics 2026-05-27 from https://api.ai-analytics.org/grant/nih/10982417. Licensed CC0.

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