# RP4: Monoclonal antibodies against henipaviruses, arenaviruses, and nairoviruses

> **NIH NIH U19** · UNIVERSITY OF TEXAS MED BR GALVESTON · 2024 · $4,640,497

## Abstract

PROJECT SUMMARY/ABSTRACT – RP4 (Monoclonal Antibodies against Henipaviruses, Arenaviruses
and Nairoviruses)
The paramyxoviruses, nairoviruses, and arenaviruses 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, which can be provided by active immunization (as in RP1 and
RP2 here) 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 these 3 major groups 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 virus 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 pathogens Lassa, Machupo, Crimean-Congo hemorrhagic fever, Hendra, and Nipah
viruses will be applied to new discovery campaigns for related viruses in the same family or genera, as a model
for applying “plug and play” Test Cases for the prototype pathogen approach. Identifying antibodies to the related
pathogens, will validate the prototype pathogens approach, preparing us for an unexpected epidemic of a
previously unknown paramyxovirus, nairovirus, or arenavirus. Also, these programs 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 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 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 best-in-class
mAb combinations for broad and ...

## Key facts

- **NIH application ID:** 10862505
- **Project number:** 1U19AI181930-01
- **Recipient organization:** UNIVERSITY OF TEXAS MED BR GALVESTON
- **Principal Investigator:** James E Crowe
- **Activity code:** U19 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2024
- **Award amount:** $4,640,497
- **Award type:** 1
- **Project period:** 2024-07-30 → 2027-06-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10862505

## Citation

> US National Institutes of Health, RePORTER application 10862505, RP4: Monoclonal antibodies against henipaviruses, arenaviruses, and nairoviruses (1U19AI181930-01). Retrieved via AI Analytics 2026-05-24 from https://api.ai-analytics.org/grant/nih/10862505. Licensed CC0.

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