# Antibody therapeutics for human viral hemorrhagic fevers and prevention of late neurological syndromes

> **NIH NIH DP5** · HARVARD MEDICAL SCHOOL · 2020 · $423,750

## Abstract

PROJECT SUMMARY
Filoviruses that circulate in the Eastern Hemisphere and several arenaviruses that
circulate in the Western hemisphere cause human hemorrhagic fevers with case fatality
rates (15% to 90%). Most lack treatment options. The research project proposed here is
an effort to use the blood of survivors of viral hemorrhagic fevers to understand the basic
molecular features, on both the human host and pathogen side, that make transfusion of
antibodies (passive immunity) more or less effective in treating human viral hemorrhagic
fevers. To achieve this goal, we propose to compare the human antibody response to
filoviruses and arenaviruses. We chose to compare both groups of viruses because for
Junín virus infection, transfusion of survivor plasma is highly effective and routinely used
clinically – it decreases the case fatality rate of infection to less than 1%. In contrast,
while passive immunity has also shown promise in animal models against Ebola virus,
particularly with the use of a three antibody-cocktail called ZMapp®, it has yet to be
clearly demonstrated as effective in humans. We have recruited survivors of Junín virus,
Ebola virus, and Marburg virus infections for blood donation. In Aim 1, we will recover the
genes encoding antibodies that react against the arenavirus and filovirus surface
glycoprotein (the target of antibodies) from the blood of these survivors. With the
sequences of antibody genes, we will produce large quantities of each identified antibody
as recombinant proteins and study these in binding and viral neutralization assays. In Aim
2, we will determine antibody-glycoprotein structure using X-ray crystallography and cryo-
electron (Cryo-EM) microscopy. In Aim 3, we will study the antibodies' non-neutralizing
antiviral activity in cell-based assays and in small animal models working closely with our
collaborators. We will also determine if we can alleviate a known side effect of passive
immunity against Junín virus – development, in 10% of treated survivors, of a late
neurological syndrome that probably occurs because of viral replication in their central
nervous system. The basic findings from our research will help us design the next
generation of passive immunity strategies against emerging viruses that cause severe
human diseases – that is, specifically tailored monoclonal antibody therapies in which
purified antibodies of known activity are included.

## Key facts

- **NIH application ID:** 9991956
- **Project number:** 5DP5OD023084-05
- **Recipient organization:** HARVARD MEDICAL SCHOOL
- **Principal Investigator:** Jonathan Abraham
- **Activity code:** DP5 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $423,750
- **Award type:** 5
- **Project period:** 2016-09-22 → 2021-08-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/9991956

## Citation

> US National Institutes of Health, RePORTER application 9991956, Antibody therapeutics for human viral hemorrhagic fevers and prevention of late neurological syndromes (5DP5OD023084-05). Retrieved via AI Analytics 2026-05-26 from https://api.ai-analytics.org/grant/nih/9991956. Licensed CC0.

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