# Isolation of broadly protective monoclonal antibodies for Crimean Congo Hemorrhagic Fever

> **NIH NIH R01** · UNIVERSITY OF MARYLAND BALTIMORE · 2024 · $685,980

## Abstract

Background/Rationale: Crimean-Congo Hemorrhagic Fever (CCHF) is the most widely distributed tick-borne
viral hemorrhagic fever infection in the world. CCHF is potentially fatal and there is currently no vaccine or
specific therapy for this disease. Monoclonal antibodies (mAbs) have been discovered that have shown ability
to protect; however, their limited protective breadth are a liability.
Objectives: The premise of this grant is that the humoral response raised against natural CCHF infection in
humans leads to antibody responses that can be protective. The hypothesis is that cross-protective anti-
CCHFV mAbs can be found and isolated from humans. We have data demonstrating that mouse monoclonal
antibodies can be protective, and have isolated GP38 and GC mAbs from humans. The specific aims of this
proposal are 1) Develop a cohort of CCHF survivors and isolate a panel of monoclonal antibodies against
CCHFV envelope subjects with broad responses to Gc, Gn, and/or GP38. 2) Test the efficacy of anti-CCHFV
envelope mAbs for their ability for cross-clade protection in a lethal mouse model. 3) Define the fine specificity
of the broadly protective human mAb(s) against CCHFV.
Methods: We will develop a cohort, analyze blood samples from 120 CCHF survivors in Turkey, and identify
the patients with the broadest breadth and neutralization, and undertake a detailed isolation and
characterization of up to 75 anti-CCHFV glycoprotein antibodies. Nine antibodies will then be selected for
sequential efficacy testing in the IFNAR-/- mouse model in up to five separate strains representing different
clades to identify broadly cross-protective mAbs. Four cross-protective mAbs will be chosen for fine epitope
mapping. Monoclonal antibodies in complex with a variety of CCHFV antigens will undergo x-ray
crystallography and cryo-EM.
Impact: If our hypothesis proves correct, the isolation of human monoclonal antibodies that are cross-protective
will represent a breakthrough, and will be candidates for further pre-clinical and clinical testing. In addition, the
identification of an epitope would have implications for vaccine design against this virus.

## Key facts

- **NIH application ID:** 10981217
- **Project number:** 1R01AI180125-01A1
- **Recipient organization:** UNIVERSITY OF MARYLAND BALTIMORE
- **Principal Investigator:** Mohammad Mohseni Sajadi
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2024
- **Award amount:** $685,980
- **Award type:** 1
- **Project period:** 2024-07-23 → 2029-06-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10981217

## Citation

> US National Institutes of Health, RePORTER application 10981217, Isolation of broadly protective monoclonal antibodies for Crimean Congo Hemorrhagic Fever (1R01AI180125-01A1). Retrieved via AI Analytics 2026-05-25 from https://api.ai-analytics.org/grant/nih/10981217. Licensed CC0.

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