# Analysis of a novel Crimean-Congo hemorrhagic fever vaccine and its mechanism of protection in rodent models

> **NIH NIH R01** · THOMAS JEFFERSON UNIVERSITY · 2022 · $779,687

## Abstract

Crimean-Congo hemorrhagic fever virus (CCHFV) causes severe disease in humans, with fatality rates reaching
40%. CCHFV is endemic to parts of Africa, Asia, the Middle East, and Europe, specifically to regions where the
tick vector, species of the Hyalomma genus, is present. Classified as an NIH/NIAID Category A and WHO high-
priority pathogen, CCHFV poses the highest possible risk to national security and public health. CCHFV is a
negative-sense single-stranded RNA virus in the order Bunyavirales. CCHFV is an Emerging Infectious Disease,
posing a high risk of a widespread outbreak. An inactivated whole virus vaccine was the only CCHFV vaccine to
be tested in humans and was ineffective. We propose the use of inactivated rabies virus (RABV)- and vesicular
stomatitis virus (VSV)-based CCHFV vaccines, as inactivated rhabdoviral vectors have not yet been explored.
Inactivated rhabdoviral-based vaccines are safe and effective at inducing immunity and protection against
multiple hemorrhagic fever viruses, and a VSV-based surrogate challenge virus is an effective tool in another
hemorrhagic fever model. The goal of this project is two-fold: first, to compare RABV- and VSV-based
CCHFV/RABV bivalent vaccines in terms of their production, immunogenicity; second, to establish a non-BSL-4
VSV-based surrogate mouse challenge system for CCHFV to determine mechanism of protection.
 We hypothesize that inactivated rhabdoviral-based CCHFV vaccines will protect against the
CCHFV challenge through non-neutralizing antibodies directed against GP38.
Toward this hypothesis, we propose three Aims:
 Aim 1: Characterization of Rhabdoviral-based CCHFV vaccine constructs.
This aim does characterize and test the immunogenicity of RABV- and VSV-based CCHFV vaccines and
compare them to the Bulgaria human vaccine and an mRNA-based vaccine provided by collaborators.
 Aim 2: Determine rhabdoviral-based CCHFV vaccine mechanism of protection by establishing a
surrogate challenge virus model.
This aim aims to develop a non-BSL-4-requiring surrogate challenge model for CCHFV and compare it to the
established BSL-4 WT CCHFV model in vaccine efficacy studies.
 Aim 3: Evaluate the protective efficacy of rhabdoviral-based vaccine candidates in a wildtype
CCHFV lethal challenge model using needle and tick challenge.
The goal of this aim is to determine the efficacy of our rhabdoviral-based vaccines and control vaccines against
WT CCHFV challenge in two different lethal challenge model.

## Key facts

- **NIH application ID:** 10520741
- **Project number:** 1R01AI167295-01A1
- **Recipient organization:** THOMAS JEFFERSON UNIVERSITY
- **Principal Investigator:** Dennis A Bente
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2022
- **Award amount:** $779,687
- **Award type:** 1
- **Project period:** 2022-08-25 → 2026-07-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10520741

## Citation

> US National Institutes of Health, RePORTER application 10520741, Analysis of a novel Crimean-Congo hemorrhagic fever vaccine and its mechanism of protection in rodent models (1R01AI167295-01A1). Retrieved via AI Analytics 2026-05-26 from https://api.ai-analytics.org/grant/nih/10520741. Licensed CC0.

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