# Human monoclonal antibodies for hantaviruses

> **NIH NIH U19** · VANDERBILT UNIVERSITY MEDICAL CENTER · 2024 · $4,790,125

## Abstract

PROJECT SUMMARY – RP4
The hantaviruses represent collections of diverse virus species, and these groups of viruses are ideal for
prototype pathogen immunity approaches. The goal of developing medical countermeasures is to confer
protective immunity to hantaviruses, which can be provided by active immunization (as in our BP4 consortium
RP3 colleagues) or by passive immunization with long-acting (90-day half-life) monoclonal antibodies (mAbs).
In this RP4, we will used several different state-of-the-art antibody discovery approaches to isolate and
engineer optimal mAbs for this major of viruses. Virus-immune B cells will be interrogated with several well-
developed human mAb discovery platforms, including high-throughput single cell sorting and single cell
RNAseq techniques, or converted to stable human hybridoma cell lines. B cell line supernatants or
recombinant mAbs will be subjected to high-throughput screening to identify Abs that bind to hantavirus
surface proteins and functionally inhibit virus replication. Our objectives include determining the principles
governing optimal mAb combinations and synergy, developing new in vitro selection methods to enhance
antibody neutralization potency and breadth, and genetically modifying mAbs for extended-half-life properties
to enable the use of injections of long-lived antibodies to confer protective immunity and protection like that of
vaccines. Lessons learned in the year 1 to 3 studies of the prototype viruses Sin Nombre virus (SNV) and
Andes virus (ANDV) will be applied to new discovery campaigns for related viruses in the same family or
genera. We will focus these efforts on Hantaan virus as a model for applying Test Cases for the prototype
pathogen approach. Identifying antibodies to Hantaan virus will validate the prototype pathogens approach,
preparing us for an unexpected epidemic of a previously unknown hantavirus or other bunyavirus. Also, this
program will isolate promising medical countermeasures for additional potential causes of future epidemics.
Further, incorporating screens for wide breadth of recognition in these studies may enable identification of pan-
family or pan-genus antibodies that can but used for multiple related agents, including future related pathogens
for which we have not yet specifically prepared. Identifying major sites of vulnerability on the virus surface Gn-
Gc proteins for recognition by neutralizing and/or protective antibodies also will be useful for our consortium
partners working on antigen design. Prioritized mAbs then will be tested for therapeutic efficacy in multiple
animal models of infection. The lead mAbs will be selected, and CHO cell lines will be made by our industry
partner IDBiologics for Ab production, in preparation for cGMP manufacture and IND planning. The work
promises to yield best-in-class mAb combinations for broad and potent activity against hantaviruses that can
be used to treat or prevent human virus infections. These studies will ident...

## Key facts

- **NIH application ID:** 10863662
- **Project number:** 1U19AI181979-01
- **Recipient organization:** VANDERBILT UNIVERSITY MEDICAL CENTER
- **Principal Investigator:** James E Crowe
- **Activity code:** U19 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2024
- **Award amount:** $4,790,125
- **Award type:** 1
- **Project period:** 2024-08-20 → 2027-07-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10863662

## Citation

> US National Institutes of Health, RePORTER application 10863662, Human monoclonal antibodies for hantaviruses (1U19AI181979-01). Retrieved via AI Analytics 2026-05-24 from https://api.ai-analytics.org/grant/nih/10863662. Licensed CC0.

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