# Transfusion-related immunomodulation influences infectious disease outcomes

> **NIH NIH R01** · VITALANT · 2020 · $604,784

## Abstract

Project Summary/Abstract
Transmission of acute viral infections through blood transfusion during large epidemics is a serious public
health issue, particularly for newly emerging infections for which no sensitive FDA-approved tests are
available. Arboviruses can be serious acute infections leading to serious long-term complications, and are
noted for their massive epidemic, as recently demonstrated with first chikungunya virus (CHIKV) and then Zika
virus. Despite possessing many of the characteristics required for blood transfusion transmission (TT), such as
high loads of infectious virus in blood and the ability to infect via intravenous inoculation, there have never
been any CHIKV TT events reported. This is despite large-scale epidemics where up to 2% of blood donations
have been found to be RNA reactive. We have preliminary data supporting the fact that CHIKV can be
transfusion-transmitted in mice, and that transfusion of RBC attenuated CHIKV pathogenesis. The central
hypothesis behind this study is that TT does occur, however a number of factors drive infection
towards being asymptomatic or mild. Further, immune modulation during transmission, in this case via the
blood transfusion itself, leads to an attenuation of disease. Specifically, we and others have demonstrated a
number of innate immune factors are both modulated by transfusion and able to alter CHIKV outcomes. These
include innate lymphoid cells and regulatory T cells and the cytokines both upstream and downstream of their
stimulation. This study will use a murine model of CHIKV pathogenesis to investigate these findings further.
Additionally, it will mimic blood transfusions, TT of CHIKV, and study immune parameters and disease
outcomes. Beyond understanding the interplay between pathogenesis and blood transfusion, these studies will
have a wider impact on acute viral infections in general. It is likely that similar immune factors can have
dramatic effects on viral replication and/or pathogenesis, and thus a deeper understanding of how these
mechanisms are mediated will allow better planning for screening efforts and potentially even interventions
during serious epidemics. This will allow improved capabilities and decision making in responding rapidly to a
new viral threat to blood safety and availability.

## Key facts

- **NIH application ID:** 10034518
- **Project number:** 1R01HL153073-01
- **Recipient organization:** VITALANT
- **Principal Investigator:** GRAHAM SIMMONS
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $604,784
- **Award type:** 1
- **Project period:** 2020-09-01 → 2024-06-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10034518

## Citation

> US National Institutes of Health, RePORTER application 10034518, Transfusion-related immunomodulation influences infectious disease outcomes (1R01HL153073-01). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/10034518. Licensed CC0.

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