# Administrative Supplement: Stratifying Patient Immune Endotypes in Sepsis (SPIES Study)

> **NIH NIH R01** · UNIVERSITY OF FLORIDA · 2022 · $424,705

## Abstract

ABSTRACT
Sepsis remains the leading cause of hospital mortality today. Despite its increasing incidence due to an aging
population with greater comorbidities, in-hospital mortality has significantly declined over the past decade. This
is due in large part to earlier recognition and better compliance with best practices in early sepsis management.
Despite improved in-hospital mortality, a large proportion (up to 50% in some studies) of sepsis survivors never
fully recover and develop chronic critical illness (CCI), characterized by persistent immune suppression,
recurrent infections, sepsis recidivism and poor long-term outcomes. There are three key challenges, however,
hindering the development of immunological therapies in these sepsis survivors: i) how to endotype patients with
sepsis who are immunosuppressed; ii) how to quantify the degree of immune suppression; and iii) how to identify
promising immune stimulants in individual immunosuppressed patients? We believe that current efforts to
endotype sepsis survivors as being immunosuppressed have not been fully successful because they fail to
directly assess immune function, instead using either genomic or proteomic measures of immune status. Here
we propose to: 1) assess whether stimulated T cell production of IFN-γ and stimulated monocyte production
of TNFα, as quantitated by ELISpot, better predicts infectious and long-term outcomes in sepsis survivors
than common static measurements based on protein levels, expression and nucleic acid concentrations; and
2) to employ ELISpot assessment of IFN-γ production by T-cells and TNFα production by monocytes from
sepsis survivors to examine ex vivo the comparative efficacy of different immune stimulants to reverse sepsis-
induced immunosuppression. Under the original award, we proposed a prospective, observational trial of 270
patients with sepsis (using Sepsis-3 criteria) compared to 90 patients with critical illness without sepsis (total
of 390 with 30 healthy subjects for quality control and validation) at 3 academic institutions. Here in this
supplement application for the first year, we propose to add 30 trauma and 15 burn patients, although
over the life of the parent grant, we hope to enroll 60 trauma patients and 45 burn patients. At 1, 4 and
7 days post sepsis, trauma or critical illness diagnosis (7 and 14 days in burns), blood samples will be
obtained and blood T-cell and monocyte production of IFN-γ and TNFα, respectively, will be determined by
ELISpot. Secondary infections will be the primary clinical index of outcome, with secondary indices including
hospital readmission, and 180-day mortality. In addition, we will evaluate in this ELISpot platform the ex
vivo response of IFN-γ production by T-cells and TNFα production by monocytes stimulated with
varying concentrations of immune stimulants are currently under consideration as potential therapeutics
for sepsis patients. This application proposes the validation of a novel functional bioas...

## Key facts

- **NIH application ID:** 10683437
- **Project number:** 3R01GM139046-03S1
- **Recipient organization:** UNIVERSITY OF FLORIDA
- **Principal Investigator:** LYLE L MOLDAWER
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2022
- **Award amount:** $424,705
- **Award type:** 3
- **Project period:** 2020-09-05 → 2025-06-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10683437

## Citation

> US National Institutes of Health, RePORTER application 10683437, Administrative Supplement: Stratifying Patient Immune Endotypes in Sepsis (SPIES Study) (3R01GM139046-03S1). Retrieved via AI Analytics 2026-05-26 from https://api.ai-analytics.org/grant/nih/10683437. Licensed CC0.

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