# Role of IgE in human disease and immunity to ticks

> **NIH NIH R01** · VANDERBILT UNIVERSITY MEDICAL CENTER · 2024 · $763,421

## Abstract

PROJECT SUMMARY
There is a growing body of evidence that the allergic immune response is directed toward ectoparasites,
like it is helminths (endoparasites), possibly playing a central role in the phenomenon known as acquired
tick resistance. We hypothesize that human immunity naturally develops following recurrent tick bites,
involves IgE antibodies that target tick salivary proteins, and can result in either IgE-mediated disease
(alpha-gal syndrome) and/or protection from subsequent bites. At the center of the IgE-mediated immune
response is the IgE antibody molecule. In sensitized individuals, re-exposure to the offending antigen
results in IgE engagement, causing Fcε receptor cross-linking and activation of mast cells and basophils.
This triggers the release of mediators into the local tissue, resulting in the mass influx of basophils and
eosinophils. A novel way to study allergic immunity is to use naturally occurring human IgE monoclonal
antibodies (mAbs), isolated from allergic or parasite exposed subjects. We have established a method to
grow, identify and immortalize ultra-rare IgE encoding memory B cells by making human hybridomas
from the peripheral blood of allergic and parasitized individuals. Using our technology, we will generate
IgE mAbs from human subjects with alpha-gal syndrome and/or have received numerous recurrent tick
bites in Aim 1. We believe that IgE expressing B cell clones targeting tick salivary antigens are present
and can be captured from human subjects exposed to tick bites as part of their natural defense against
parasites. Already our preliminary data shows this to be the case, humans exposed to tick bites develop
IgE antibodies to tick salivary antigens. We will in Aim 2 identify, express, and validate the specific tick
salivary protein targeted by each tick-specific human IgE antibody through immunoprecipitation and
proteomics analyses using partially fed tick salivary extracts. We believe that alpha-gal is a very small
fraction of the antigens that the human IgE antibody response is targeting when one is bitten repeatably
by ticks and exposed to their salivary proteins. We will use these human mAbs and their tick salivary
antigens in Aim 3 to characterize the role IgE plays in immunity to tick bites using murine models of
passive systemic anaphylaxis and active tick feeding challenges. Analyses of the bite wound infiltrates
and rates of tick feeding success will allow for careful direct measures of the IgE-mediated immune
response between experimental and control animals. To begin studies to understand human immunity to
ticks, we first must define the dominant immune targets that could allow for interruption of tick feeding
and perhaps pathogen transmission. This work will have tremendous implications in studies of
pathogenesis and immunity of tickborne diseases, such as establishing correlates of protection against tick
feeding in humans, and indirectly, the transmission of infectious pathogens and disease.

## Key facts

- **NIH application ID:** 10858302
- **Project number:** 1R01AI182247-01
- **Recipient organization:** VANDERBILT UNIVERSITY MEDICAL CENTER
- **Principal Investigator:** Scott Alan Smith
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2024
- **Award amount:** $763,421
- **Award type:** 1
- **Project period:** 2024-03-20 → 2029-01-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10858302

## Citation

> US National Institutes of Health, RePORTER application 10858302, Role of IgE in human disease and immunity to ticks (1R01AI182247-01). Retrieved via AI Analytics 2026-05-24 from https://api.ai-analytics.org/grant/nih/10858302. Licensed CC0.

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