# Immunometabolic signatures of BCG-induced neonatal trained immunity

> **NIH NIH K08** · BETH ISRAEL DEACONESS MEDICAL CENTER · 2024 · $175,572

## Abstract

Project Summary/Abstract
This proposal presents a 5-year research career development program focused on the study of Bacille Calmette-
Guérin (BCG) vaccine and the mechanisms of innate immune memory, otherwise known as trained immunity,
underlying its observed, pathogen-agnostic, protective health effects in early life. The candidate is currently an
Instructor of Pediatrics at Harvard Medical School in the Department of Neonatology at Beth Israel Deaconess
Medical Center, and Associate Scientist at the Precision Vaccines Program in Boston Children’s Hospital (BCH).
The outlined proposal builds on the candidate’s previous research on in vitro modeling of human leukocyte
responses to BCG vaccine formulations and complements her clinical training as a Neonatologist. Under the
mentorship of Dr. Ofer Levy, a human immunology and vaccinology expert at BCH, and complementary guidance
by an Advisory Committee, the candidate will characterize novel immunometabolic mechanisms of BCG vaccine-
induced trained immunity in newborns. The proposed experiments and didactic work will provide the candidate
with a unique intellectual framework and skill set at the intersection of newborn immunology, trained immunity
and systems biology that will facilitate her transition to independence as a translational pediatric vaccinologist.
Infectious diseases are leading causes of neonatal morbidity and mortality, due in part to a distinct immune
system at this developmental stage. The live attenuated Mycobacterium bovis vaccine BCG is given at birth to
millions of newborns worldwide to prevent severe forms of tuberculosis (TB). Epidemiologic studies demonstrate
that BCG confers a mortality benefit to immunized newborns when administered early in life, attributed to
protection vs. non-TB respiratory infections and sepsis. The mechanisms underlying BCG beneficial health
effects in early life are incompletely characterized, while in adults epigenetic and metabolic reprogramming of
monocytes have been implicated. This proposal will investigate the immunometabolic signatures of BCG-induced
trained immunity in human newborns, who manifest distinct immunity and bioenergetic demands. The proposed
study is based on preliminary data demonstrating distinct immunometabolic rewiring in human newborns and
their leukocytes after BCG immunization producing key age-specific signatures of BCG-induced trained
immunity. More specifically, the aims of this proposal are to: 1) Characterize BCG-induced immunometabolic
pathways of trained immunity in human newborn monocytes using a novel in vitro platform established by the
candidate; 2) Leverage an in vivo cohort to identify and validate metabolic pathways that may drive trained
immunity in BCG-immunized human neonates; and 3) Mechanistically probe age-specific metabolic pathways of
BCG-induced trained immunity in vitro.
The proposed project, linking expertise in neonatology, immunology, metabolism, vaccinology and systems
biology will dissect cel...

## Key facts

- **NIH application ID:** 10883577
- **Project number:** 5K08AI168487-02
- **Recipient organization:** BETH ISRAEL DEACONESS MEDICAL CENTER
- **Principal Investigator:** Asimenia Angelidou
- **Activity code:** K08 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2024
- **Award amount:** $175,572
- **Award type:** 5
- **Project period:** 2023-07-06 → 2028-06-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10883577

## Citation

> US National Institutes of Health, RePORTER application 10883577, Immunometabolic signatures of BCG-induced neonatal trained immunity (5K08AI168487-02). Retrieved via AI Analytics 2026-05-24 from https://api.ai-analytics.org/grant/nih/10883577. Licensed CC0.

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