# Characterizing the human antibody response to henipavirus infection

> **NIH NIH F31** · VANDERBILT UNIVERSITY · 2020 · $30,231

## Abstract

Project Summary
RNA viruses comprise some of the most deadly human pathogens described to date, with new agents
constantly emerging as humans encroach on once untouched ecosystems. Two such viruses, Hendra (HeV)
and Nipah (NiV), were first described in 1994 and 1998, respectively, and have causes sporadic outbreaks of
disease in humans in Australia and Southeast Asia. Recently, though, Nipah virus has begun spreading
geographically into new regions of India, causing disease with mortality rates reaching close to 100%. Because
of the ability to cause such high morbidity and mortality, coupled with the fact that human-to-human
transmission has been observed with Nipah virus, the WHO designated these agents as priority diseases in
2018, with urgent needs for accelerated research and development of vaccines and therapeutics. Despite this
urgency, no treatments or vaccines have been licensed to date to combat these viruses, and major gaps in
knowledge surrounding the human immune response to Hendra and Nipah exist. The overarching goal of this
proposal is to elucidate the molecular and structural mechanisms of neutralization by human monoclonal
antibodies targeting the attachment glycoproteins of Hendra and Nipah viruses. I have isolated a large panel of
monoclonal antibodies from a human subject inoculated with the Hendra equine vaccine and have shown that
these antibodies bind to the attachment glycoproteins or Hendra and/or Nipah viruses. A subset of antibodies
potently neutralize both Hendra and Nipah virus isolates. My central hypothesis is that human antibodies
targeting the henipavirus attachment glycoprotein neutralize by blocking receptor attachment and/or preventing
fusion. In Aim 1, I will use a flow cytometric assay and pre- and post-attachment neutralization tests with
chimeric Cedar virus bearing Hendra or Nipah virus glycoproteins to determine the molecular mechanisms by
which antibodies neutralize virus. I will elaborate on these findings in Aim 2 by using a variety of structural and
biochemical techniques to map the antigenic sites on the henipavirus attachment glycoprotein, with an
emphasis on antigenic sites that elicit potently neutralizing, cross-reactive antibodies. My studies to date
suggest the most potent antibodies able to bind both Hendra and Nipah virus attachment glycoproteins
function by blocking viral attachment to the host receptor ephrin-B2, but that at least one other distinct
antigenic site elicits neutralizing antibodies that use a distinct mechanism to neutralize virus. This proposal will
provide insight into the human humoral response to henipavirus infection and will help to rationally guide the
design of vaccines and antibody therapeutics.

## Key facts

- **NIH application ID:** 9989464
- **Project number:** 1F31AI152332-01
- **Recipient organization:** VANDERBILT UNIVERSITY
- **Principal Investigator:** Michael P Doyle
- **Activity code:** F31 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $30,231
- **Award type:** 1
- **Project period:** 2020-03-01 → 2023-02-28

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/9989464

## Citation

> US National Institutes of Health, RePORTER application 9989464, Characterizing the human antibody response to henipavirus infection (1F31AI152332-01). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/9989464. Licensed CC0.

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