# Preclinical evaluation of a potent Lassa fever immunotherapeutic antibody cocktail

> **NIH NIH R01** · TULANE UNIVERSITY OF LOUISIANA · 2021 · $1,124,215

## Abstract

“Preclinical evaluation of a potent Lassa fever immunotherapeutic antibody cocktail”
ABSTRACT
Lassa fever is an often-fatal viral hemorrhagic fever (VHF) that is endemic in West Africa where it causes
significant social and economic disruption. The lack of an approved therapeutic or vaccine, potential for
geographic expansion of the rodent reservoir, ease of procurement and weaponization of the virus, and the
recent emergence of new Lassa virus (LASV) strains support recommendations for enhanced preparedness
for Lassa fever (LF). We isolated and characterized over 113 human monoclonal antibodies (MAbs) from
memory B cells of Lassa fever survivors, the first large panel of human MAbs against LASV described. We
found that the most potent neutralizing hMAbs target quaternary epitopes that require both GP1 and GP2
subunits of each monomer in the trimer. LASV is genetically diverse with four distinct lineages present in
West Africa. Some hMAbs neutralized all four LASV lineages. Bicistronic IgG1 backbone vectors for high
level stable expression in mammalian cells were used to generate sufficient quantities of the neutralizing
hMAbs (BNhMAbs) for therapeutic evaluation using the CHOLCelect system
(www.zalgenlabs.com/technology.html). Challenge of outbred guinea pigs (GP) in a model of lethal LF
informed the down-selection of BNhMAbs for studies in a nonhuman primate (NHP) model, Cynomolgus
macaques. A combination of three BNhMAbs, each with broad neutralizing activity and recognition of distinct
epitopes on the LASV glycoprotein complex, rescued 100% of NHPs even after delay in the start of treatment
to 8 days post-infection, a time when the animals displayed severe hematological and metabolic
dysregulation. Our proposed project meets the strict requirements of RFA-AI-16-034 in that the LASV
BNhMAb combo is a previously-identified, well-characterized, candidate therapeutic against an NIAID listed
emerging pathogen, LASV. The project will address a particular interest of RFA-AI-16-034 for
immunotherapeutics that would “enable prevention of infection or intoxication in the face of an immediate
threat, protection of immunocompromised individuals, or post-exposure treatment to suppress infection and
disease.” We have named the LASV BNhMAb immunotherapeutic cocktail “Arevirumab” based on guidance
from the International Nonproprietary Name (INN) Working Group and the USAN Council (USANC) on
monoclonal antibody nomenclature scheme language guidelines. In Milestone 1 we will perform dose finding
and dosing interval studies with single LASV BNhMAbs and Arevirumab therapy in guinea pigs and
Cynomolgus macaques, both established models of lethal Lassa fever. Chemistry, Manufacturing and
Control (CMC) data will be generated in Milestone 2. In Milestone 3 we will perform preclinical pharmacology
and toxicology of Arevirumab in appropriate animal models. At the conclusion of the proposed program we
will enter clinical evaluation of a first-in-class immunotherapeutic...

## Key facts

- **NIH application ID:** 10176382
- **Project number:** 5R01AI132223-05
- **Recipient organization:** TULANE UNIVERSITY OF LOUISIANA
- **Principal Investigator:** Robert F Garry
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2021
- **Award amount:** $1,124,215
- **Award type:** 5
- **Project period:** 2017-06-26 → 2024-05-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10176382

## Citation

> US National Institutes of Health, RePORTER application 10176382, Preclinical evaluation of a potent Lassa fever immunotherapeutic antibody cocktail (5R01AI132223-05). Retrieved via AI Analytics 2026-05-24 from https://api.ai-analytics.org/grant/nih/10176382. Licensed CC0.

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