# Project 2 - Vanderbilt University

> **NIH NIH U19** · HENRY M. JACKSON FDN FOR THE ADV MIL/MED · 2021 · $554,565

## Abstract

Project Summary
The Henipavirus genus of RNA viruses in the family Paramyxoviridae contains five established species.
Henipaviruses are found naturally in bats in Australia and Asia and more recently have been found in Africa,
and they have a wide host range. These zoonotic pathogens can cause severe illness and death in domestic
animals and humans. The prophylactic and therapeutic options for Hendra and Nipah virus infections in man
are limited. Anti-Hendra/Nipah human mAbs are expected to be valuable antiviral therapeutics as
countermeasures to Hendra and Nipah virus disease in humans. Here, we will isolate panels of naturally
occurring human monoclonal antibodies (mAbs) that bind cross-reactively to both Hendra and Nipah virus F or
G proteins and neutralize both viruses. In preliminary experiments, we have isolated some mAbs that exhibit
very high potency in neutralization assays, suggesting they have high potential as prophylactic and therapeutic
molecules for humans. We propose here a series of aims that will contribute significantly to the development
and characterization of such human mAbs reactive to the F and G glycoproteins of Hendra and Nipah virus in
preparation for clinical studies. The work will identify and fully characterize a panel of highly promising
antibodies with the goal of identifying and selecting lead compounds and advancing their preclinical
development. The work is organized in two major Specific Aims: Aim 1) Isolation of human mAbs from patients
previously infected with henipavirus or exposed to henipavirus vaccine antigens. In this Aim, human mAbs will
be identified that recognize epitopes that are conserved across henipaviruses and neutralize those viruses at
low concentration. Blood cells from a subject exposed to Hendra virus equine vaccine will be screened for virus
specific antibodies. These cells will be converted to stable human hybridoma cell lines and subjected to high-
throughput screening to identify Abs that bind to Hendra and Nipah G proteins and functionally inhibit virus
replication. Aim 2: Develop Abs for the treatment of henipavirus infections. Antibodies identified in Aim 1 will be
tested for their broad recognition of conserved epitopes across all henipaviruses and for their ability to
neutralize in culture. Prioritized antibodies then will be tested for therapeutic efficacy in multiple animal models
of infection including nonhuman primates. The leads will be selected, and CHO cell lines will be made by Mapp
Biopharmaceutical for Ab production, in preparation for cGMP manufacture and IND planning. The work
promises to yield a best-in-class antibody preparation for broad and potent activity against henipaviruses that
can be used to treat or prevent human henipavirus infections.

## Key facts

- **NIH application ID:** 10119244
- **Project number:** 5U19AI142764-03
- **Recipient organization:** HENRY M. JACKSON FDN FOR THE ADV MIL/MED
- **Principal Investigator:** James E Crowe
- **Activity code:** U19 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2021
- **Award amount:** $554,565
- **Award type:** 5
- **Project period:** 2019-03-20 → 2024-02-29

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10119244

## Citation

> US National Institutes of Health, RePORTER application 10119244, Project 2 - Vanderbilt University (5U19AI142764-03). Retrieved via AI Analytics 2026-05-24 from https://api.ai-analytics.org/grant/nih/10119244. Licensed CC0.

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