# Enhancing Innate and Adaptive Immunity to Improve Sepsis Survival

> **NIH NIH R35** · WASHINGTON UNIVERSITY · 2024 · $575,370

## Abstract

Project Summary/Abstract
 Sepsis is defined as a dysregulated host inflammatory response that occurs due to life-threatening
infection with the presence of organ dysfunction. Sepsis is the most frequent cause of mortality in most
intensive care units and is responsible for over a quarter million deaths in the United States annually. The
incidence of sepsis is increasing because of the aging population and the associated weakening of the immune
system that occurs in the aged. Until recently, most research on sepsis was focused on blocking the initial
hyper-inflammatory cytokine-mediated phase of the disorder. Improved treatment protocols have resulted in
most patients surviving this initial hyper-inflammatory phase of sepsis and entering a protracted
immunosuppressive phase. The majority of deaths in sepsis occur during this immunosuppressive phase of the
disorder. Deaths in this immunosuppressive phase of sepsis are typically due to failure to control the primary
infection or a result of acquisition of secondary hospital-acquired infections, often with opportunistic pathogens
thereby underscoring the host’s impaired immunity. The reactivation of multiple latent viruses including
cytomegalovirus and herpes simplex virus that occurs in patients with protracted sepsis further attests to the
profound degree of immunosuppression in these patients. There is a growing body of evidence in animal
studies as well as data from small phase II clinical trials indicating that therapies which boost the host immune
system can improve morbidity and mortality in sepsis. This immuno-therapeutic based approach to sepsis has
been the focus of the principal investigator for over two decades. The current proposal is an extension of these
investigations.
 The overarching goal of this proposal is to identify molecular mechanisms of immunosuppression in
sepsis and develop new immuno-adjuvant therapies that restore host immunity, ameliorate organ injury, and
improve survival in sepsis. We are focusing on testing immune modulatory agents that have an excellent safety
profile and are in current clinical trials. Successful completion of this study would enable rapid translation of
newly identified drugs into clinical trials in sepsis and offer a new way forward against this heretofore
intractable disease.

## Key facts

- **NIH application ID:** 10819477
- **Project number:** 5R35GM126928-07
- **Recipient organization:** WASHINGTON UNIVERSITY
- **Principal Investigator:** Richard Samuel Hotchkiss
- **Activity code:** R35 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2024
- **Award amount:** $575,370
- **Award type:** 5
- **Project period:** 2018-05-01 → 2028-04-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10819477

## Citation

> US National Institutes of Health, RePORTER application 10819477, Enhancing Innate and Adaptive Immunity to Improve Sepsis Survival (5R35GM126928-07). Retrieved via AI Analytics 2026-05-24 from https://api.ai-analytics.org/grant/nih/10819477. Licensed CC0.

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