# Treatment of Primary Amoebic Meningoencephalitis via Modulation of Antibody Effector Functions

> **NIH NIH R01** · DUKE UNIVERSITY · 2021 · $402,500

## Abstract

Abstract:
Opportunistic CNS invasion by eukaryotic pathogens requires a highly coordinated, yet restrained, multi-
pronged immune response. CNS Infection by extracellular parasites such as Naegleria fowleri, Acanthamoeba,
and Balamuthia have proven nearly impossible to treat, yet immune directed therapies against N. fowleri have
the potential alter the course of almost universally fatal disease. The “brain eating amoeba” N. fowleri is
responsible for a devastating form of meningoencephalitis known as primary amoebic meningoencephalitis
(PAM) that is almost universally fatal (>97%) despite intensive clinical intervention, and new therapeutic
approaches are desperately needed. The protective relevance of Naegleria-reactive antibodies (Abs) in
humans is unclear, but animal models of PAM suggest that vaccinations and passive Ab administration
variably delay death and foster survival. Extracellular parasites cannot simply be neutralized by antibody, but
rather immunity relies on targeting antibody isotype specific effector mechanisms from immune cells. After
parasites are bound by antibody, isotype specific binding to fragment crystallizable receptors (FcRs) can direct
cell type specific effector functions against parasites. Prior studies of N. fowleri specific antibody responses
have not rigorously linked antibody specificity with the functional outcomes of individual\antibody isotypes,
creating a critical gap in understanding how antibody can optimally eliminate parasites from the within the
central nervous system (CNS) while not exacerbating immunopathology. We’ve generated a monoclonal Ab
specific for N. fowleri cell surface antigens that has shown strong anti-proliferative effects on parasites in vitro
and facilitates survival of infected hosts in vivo. This proposal seeks to define how combining anti-proliferative
effects of antibody and isotype specific binding can facilitate effective immune response against extracellular
CNS parasites while maintaining neuroprotection. Completion of this project will define new therapeutic
approaches to CNS infections that currently have few effective options and very poor outcomes.

## Key facts

- **NIH application ID:** 10179955
- **Project number:** 1R01NS121067-01
- **Recipient organization:** DUKE UNIVERSITY
- **Principal Investigator:** E. Ashley Moseman
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2021
- **Award amount:** $402,500
- **Award type:** 1
- **Project period:** 2021-04-01 → 2026-01-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10179955

## Citation

> US National Institutes of Health, RePORTER application 10179955, Treatment of Primary Amoebic Meningoencephalitis via Modulation of Antibody Effector Functions (1R01NS121067-01). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/10179955. Licensed CC0.

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