# Mapping the antibody response to Trypanosoma brucei variant surface glycoprotein

> **NIH NIH R21** · JOHNS HOPKINS UNIVERSITY · 2022 · $204,688

## Abstract

PROJECT SUMMARY
Trypanosoma brucei is a causative agent of human and animal African trypanosomiasis, devastating diseases
that endanger public health and present a major barrier to economic development in sub-Saharan Africa. The
extracellular parasite manages to sustain an infection in the blood and tissues of its mammalian host by
periodically “switching” its dense variant surface glycoprotein (VSG) coat. Drawing from a genomic repertoire
of ~2000 VSG-encoding genes, the parasite changes its expressed VSG coat throughout infection. Before the
host antibody response can clear a population expressing one VSG, the parasite switches expression to a new
VSG, rendering it invisible to host antibody for a time. This process occurs continually and allows the parasite
to maintain a chronic infection. The interaction between antibody and VSG, therefore, represents a critical
interface in this infection. Despite its importance, the principles governing antibody recognition of VSG remain
poorly understood. Here we propose to investigate the antibody-VSG interface during infection in high
resolution using a high-throughput epitope mapping approach called phage immunoprecipitation sequencing
(PhIP-seq). Using a phage display library containing peptides from every VSG ever annotated, we will measure
antibody responses to VSG during chronic infections, while simultaneously using a high-throughput
sequencing method developed by our lab to track the VSGs expressed during infection. In the first aim, we will
characterize the dynamics and targets of anti-VSG antibody during chronic experimental infections. In the
second aim, we will use PhIP-seq to map VSG epitopes in natural human infections. The proposed study will
further our understanding of anti-VSG antibody responses while establishing T. brucei as a tractable model for
the study of antibody responses to antigenically variable pathogens. Long term, this work could inform
strategies for diagnosis or prevention of an important neglected tropical disease.

## Key facts

- **NIH application ID:** 10527979
- **Project number:** 1R21AI163569-01A1
- **Recipient organization:** JOHNS HOPKINS UNIVERSITY
- **Principal Investigator:** Monica Mugnier
- **Activity code:** R21 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2022
- **Award amount:** $204,688
- **Award type:** 1
- **Project period:** 2022-06-03 → 2024-05-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10527979

## Citation

> US National Institutes of Health, RePORTER application 10527979, Mapping the antibody response to Trypanosoma brucei variant surface glycoprotein (1R21AI163569-01A1). Retrieved via AI Analytics 2026-05-25 from https://api.ai-analytics.org/grant/nih/10527979. Licensed CC0.

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