# A VSV vectored vaccine for emergent tick-born phleboviruses

> **NIH NIH R21** · UNIVERSITY OF PENNSYLVANIA · 2021 · $202,917

## Abstract

Vesicular stomatitis virus (VSV) is a cytopathic virus that has been developed as a vaccine
vector due to its ability to induce strong, protective antibody and T cell responses to encoded
foreign antigens after a single dose. VSV efficiently incorporates glycoproteins (
GP) from a
different virus on virion surface allowing production of replication-competent recombinant
vectors in which the cognate VSV G gene is replaced by a foreign GP gene.
Recombinant VSVs
(rVSVs) expressing foreign GPs have been studied as vaccine vectors for a number of pathogens
including the recent successful deployment of a rVSV-Ebola vaccine. Despite this success,
studies in animal models demonstrate significant pathogenic effects when some rVSV are injected
intracerebrally or when used to infect animals with defective interferon responses. Concerns
raised by these studies support development of more attenuated rVSV vectors with better safety
profiles. Specific Aim 1 will utilize a novel strategy for attenuating rVSV vaccine vectors by
joining adjacent VSV transcripts using a P2A ribosomal skipping sequence between adjacent
genes in the VSV genome. rVSV with single or multiple fused transcripts will be tested for
pathogenesis in immunocompromised mouse models or in the CNS. In Specific Aim 2 these
next generation, low pathogenicity vectors expressing the glycoproteins of Severe Fever with
Thrombocytopenia Syndrome virus (SFTSV) will be analyzed for their ability to induce
neutralizing responses. SFTSV is a pathogenic, tick-transmitted bunyaviruses that causes a
severe febrile hemorrhagic-like disease with case fatality rates of up to 30%. Initially discovered
during a 2009 outbreak of febrile illness in China, the geographic distribution of SFTSV extends
into Korea and Japan. There are currently no vaccine or therapeutics for SFTSV. Because of its
potential threat the WHO included SFTSV in its 2017 recommendation “A research and
development Blueprint for action to prevent epidemics” and identified SFTSV as one of 11 pathogens
most likely to cause severe outbreaks in the near future and proposed development of vaccines.
Included in this revised application are preliminary data demonstrating induction of strong
neutralizing antibody responses that correlate with protection from SFTSV challenge in mice
vaccinated with a 1st generation rVSV-SFTSV. Additionally, vaccination of IFNAR-/- mice with
the 1st generation rVSV-SFTSV demonstrated significant pathology (weight loss) supporting the
premise for Aim 1. This short IDEA proposal is designed to produce attenuated rVSV vectors
useful for vaccine development for many pathogens and will generate proof-of-principle data
that will permit further development of a vaccine for SFTSV.

## Key facts

- **NIH application ID:** 10117176
- **Project number:** 5R21AI142638-02
- **Recipient organization:** UNIVERSITY OF PENNSYLVANIA
- **Principal Investigator:** Paul Bates
- **Activity code:** R21 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2021
- **Award amount:** $202,917
- **Award type:** 5
- **Project period:** 2020-03-02 → 2023-02-28

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10117176

## Citation

> US National Institutes of Health, RePORTER application 10117176, A VSV vectored vaccine for emergent tick-born phleboviruses (5R21AI142638-02). Retrieved via AI Analytics 2026-05-24 from https://api.ai-analytics.org/grant/nih/10117176. Licensed CC0.

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