# Live-attenuated Rift Valley fever vaccines:  comparative mechanisms of trans-placental transmission and vaccine efficacy for developing fetuses

> **NIH NIH R01** · UNIVERSITY OF PITTSBURGH AT PITTSBURGH · 2021 · $634,557

## Abstract

PROJECT SUMMARY/ABSTRACT
 The World Health Organization warns of a pending public health emergency caused by mosquito-borne
zoonotic pathogen Rift Valley fever virus (RVFV). The consequences of this emerging virus could be
exacerbated by insufficient vaccines for prevention of infection and disease. RVF is an important
agroeconomic illness of domesticated livestock and is endemic in Africa and parts of the Middle East. Further
spread is likely given that mosquito species capable of transmitting RVFV are found in Europe and the
Americas. The most striking feature of RVF disease in sheep is a wave of fetal loss (known as an “abortion
storm”) that sweeps through herds of pregnant animals, where spontaneous abortion rates can reach as high
as 90%. Vaccination of livestock protects animals while simultaneously reducing the spread of RVFV to
people. Obstacles in the successful development of RVFV livestock vaccines include: 1) vaccine strains often
cause fetal infection and death in pregnant animals, and 2) vaccines that protect adult animals from disease
are not always effective at preventing vertical transmission during pregnancy. These hurdles represent a major
gap in the vaccine development field. The mechanisms by which live-attenuated vaccine strains of RVFV are
vertically transmitted in utero, as well as the maternal immune response required for the protection of
developing fetuses, are not known. No systematic evaluation of the vertical transmission potential of clinically-
relevant live attenuated vaccines has been performed. To address this gap in the field, we propose to use an
experimental rodent model of RVFV vertical transmission and fetal death in late-gestation pregnant rats. RVFV
directly infects the placenta in rats, causes hemorrhage and inflammation, and results in fetal malformations
including intrauterine fetal death even in pregnant dams without signs of disease. This proposal will use the
pregnant rat model to test current RVF vaccine candidates for the mechanism(s) of vertical transmission, fetal
protection, and identification of maternal immune correlates of fetal protection. We will also conduct a
comparative analysis of virulent and attenuated RVFV strains for permissivity of placental explants from
relevant species to identify cellular and structural targets of infection. Our overall hypothesis is that infection of
pregnant rats with RVFV live-attenuated vaccines will provide pre-clinical quantitative data on vaccine safety
for developing fetuses, efficacy for the fetuses, and critical maternal correlates of fetal protection. Completion
of these studies will change the paradigm of RVFV vaccine development by providing, for the first time, a
mechanistic explanation for the vertical transmission potential of clinically relevant LAVs.

## Key facts

- **NIH application ID:** 10113532
- **Project number:** 5R01AI150792-02
- **Recipient organization:** UNIVERSITY OF PITTSBURGH AT PITTSBURGH
- **Principal Investigator:** Amy L Hartman
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2021
- **Award amount:** $634,557
- **Award type:** 5
- **Project period:** 2020-03-01 → 2026-02-28

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10113532

## Citation

> US National Institutes of Health, RePORTER application 10113532, Live-attenuated Rift Valley fever vaccines:  comparative mechanisms of trans-placental transmission and vaccine efficacy for developing fetuses (5R01AI150792-02). Retrieved via AI Analytics 2026-05-25 from https://api.ai-analytics.org/grant/nih/10113532. Licensed CC0.

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