# Structure-based design of novel Lassa virus glycoproteins for vaccine development

> **NIH NIH R01** · TULANE UNIVERSITY OF LOUISIANA · 2021 · $1,172,924

## Abstract

“Structure-based design of novel Lassa virus glycoproteins for vaccine development”
ABSTRACT
Lassa fever is an often-fatal viral hemorrhagic fever (VHF) that is endemic in West Africa, and a significant
threat to public health with hundreds of thousands of annual infections. There are no approved vaccines or
therapeutics for human use. The potential for further geographic expansion of the rodent reservoirs, the ease
of procurement and weaponization of the virus, the frequent importation to North America and Europe, and
the recent emergence of novel strains in densely populated Nigeria necessitate development of broadly
reactive, fast-acting, protective vaccines. We recently determined the structure of the LASV glycoprotein
trimer in complex with neutralizing monoclonal antibodies (MAbs) derived from Lassa fever survivors. This
ground-breaking structure is the first prefusion trimer for the entire arenavirus family. This application will test
the hypothesis that this newly determined structure can guide design of novel LASV glycoproteins that
rapidly elicit broadly protective immune responses against current, antigenically diverse virus lineages. We
will now use this novel crystal structure as a design template for further stabilization of native trimers for
vaccine development. The proposed project will build on the success of a promising recombinant vesicular
stomatitis virus (rVSV) Ebola platform already in West African Ebola clinical trials. In studies proposed under
Milestone 1, we will produce a set of genetically modified, structurally stable LASV GPC constructs that
mimic native prefusion trimers and effectively present broadly neutralizing epitopes. We will construct,
validate and scale up a replication-competent, single-injection bivalent or trivalent rVSV vaccine candidate
expressing optimized LASV GPC and EBOV GP in Milestone 2. The aim of Milestone 3 is to down-select
LASV GPC constructs that elicit broad and rapid immunogenicity and superior vaccine efficacy in an outbred
guinea pig model of lethal Lassa fever. In Milestone 4, we will demonstrate that the most effective LASV
GPC-expressing vaccine candidate elicits protection against diverse lineages of LASV in cynomolgus
macaques. At the conclusion of the proposed program we will enter pre-clinical evaluation of a first-in-class
bivalent vaccine for Lassa virus and Ebola virus, the causative agents of two of the world's deadliest
hemorrhagic fevers.
This application contains proprietary/priviledged information that Tulane University and its subcontractors
request not be released to persons outside the Government, except for the purposes of review and
evaluations.

## Key facts

- **NIH application ID:** 10202410
- **Project number:** 5R01AI132244-05
- **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:** $1,172,924
- **Award type:** 5
- **Project period:** 2017-07-14 → 2024-06-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10202410

## Citation

> US National Institutes of Health, RePORTER application 10202410, Structure-based design of novel Lassa virus glycoproteins for vaccine development (5R01AI132244-05). Retrieved via AI Analytics 2026-05-24 from https://api.ai-analytics.org/grant/nih/10202410. Licensed CC0.

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