# Stratifying Patient Immune Endotypes in Sepsis (SPIES Study)

> **NIH NIH R01** · UNIVERSITY OF FLORIDA · 2024 · $720,877

## Abstract

ABSTRACT
Sepsis remains the leading cause of hospital mortality today.1 Despite its increasing incidence due to an aging
population with greater comorbidities, in-hospital mortality has significantly declined over the past decade.2 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)3-5 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
TNF 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- production by T-cells and TNF production by monocytes from sepsis
survivors to examine ex vivo the comparative efficacy of different immune stimulants to reverse sepsis-induced
immunosuppression. To achieve these goals, we propose 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. At 1, 4 and 7 days post sepsis
diagnosis, blood samples will be obtained and blood T-cell and monocyte production of IFN- and TNF,
respectively, will be determined by ELISpot. In addition, samples will be obtained for other biomarkers, including
plasma proteins (IL-6 and sPD-L1), CD14+ cell expression of HLA-DR, total lymphocyte count and whole blood
genomics. Secondary infections will be the primary clinical index of outcome6, 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- production by T-cells and TNF production by monocytes stimulated with varying
concentrations of IL-7, anti-PD-1 mAb, GITRL, OX40L or 4-1BB, using a randomized block design. These
immune stimulants are currently under consideration as potential therapeutics for sepsis patients. This
application proposes the validation of a novel functi...

## Key facts

- **NIH application ID:** 10876465
- **Project number:** 5R01GM139046-05
- **Recipient organization:** UNIVERSITY OF FLORIDA
- **Principal Investigator:** Robert Maile
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2024
- **Award amount:** $720,877
- **Award type:** 5
- **Project period:** 2020-09-05 → 2026-06-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10876465

## Citation

> US National Institutes of Health, RePORTER application 10876465, Stratifying Patient Immune Endotypes in Sepsis (SPIES Study) (5R01GM139046-05). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/10876465. Licensed CC0.

---

*[NIH grants dataset](/datasets/nih-grants) · CC0 1.0*