# Newborn cohorts to discover and validate biomarkers of neonatal vaccine immunogenicity

> **NIH NIH U19** · BOSTON CHILDREN'S HOSPITAL · 2020 · $558,074

## Abstract

PROJECT SUMMARY
Newborns are severely affected by infection. Immunization is one of the most effective strategies to prevent
infection but many vaccines do not work optimally in early life. Our understanding of the mechanisms leading
to vaccine-induced protection is early life is very limited. This relates in part to the small sample volumes
obtainable, and the fact that the host response to vaccination in the newborn is complicated by a rapidly
shifting developmental program and presence of maternal antibodies (MatAbs). Our Human Immunology
Project Consortium (HIPC) team has developed a robust protocol that allows the full force of systems
vaccinology (transcriptomics, proteomics, immune profiling; collectively called OMIC) to be applied with < 2ml
of blood. We also have developed the informatics tools to decipher the impact of rapidly changing host immune
status as well as MatAbs. Lastly, we developed in vitro platforms that enable assessment of cause-effect
relationships. We have proven the feasibility of this comprehensive approach in a pilot (Expanded Program on
Immunization Consortium; EPIC) study. We are now proposing to employ our state-of-the-art experimental
and informatics pipeline to characterize vaccine-induced molecular pathways in newborns correlating with
hepatitis B vaccine (HBV) immunogenicity. HBV was chosen as the model, because it is the only newborn
vaccine with a clearly established, quantifiable correlate of protection (CoP).
The goal of the Clinical Core (CC) is to define the impact on HBV responses of both basal characteristics
(immune status, MatAbs, etc) and of co-administration of Bacille Calmette-Guérin (BCG) vaccine. Enrollment
of newborns for a training- and test-set of samples at the Medical Research Council (MRC)-Gambia (CC-Site
1) will be followed by validation of key signatures in a cohort in Papua New Guinea (PNG; CC-Site 2). Given
their longstanding and proven track records, both CC-Sites are particularly well suited to conduct these
studies. Across both CCs, we will use identical vaccines, clinical and laboratory protocols and reagents. We
approach this via 4 Specific Aims: 1) Enroll well-defined cohorts of Gambian newborns for in vivo OMIC
profiling and in vitro responses following immunization with HBV ± BCG; 2) Measure adaptive immune
responses to HBV, enabling correlation of in vivo OMIC signatures and in vitro vaccine modeling assays with
established CoP; 3) Measure MatAbs in relation to vaccine-induced neonatal and infant OMIC vaccine
signatures and adaptive responses; 4) Validate key signatures identified in a distinct independent PNG
newborn cohort. Overall, the proposed CC will enable characterization and validation of vaccine-induced OMIC
signatures and assessment of their potential to predict CoP. These studies will ultimately define mechanisms
that will inform development of vaccine formulations optimized for early life immunization.

## Key facts

- **NIH application ID:** 9822172
- **Project number:** 5U19AI118608-04
- **Recipient organization:** BOSTON CHILDREN'S HOSPITAL
- **Principal Investigator:** OFER LEVY
- **Activity code:** U19 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $558,074
- **Award type:** 5
- **Project period:** — → —

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/9822172

## Citation

> US National Institutes of Health, RePORTER application 9822172, Newborn cohorts to discover and validate biomarkers of neonatal vaccine immunogenicity (5U19AI118608-04). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/9822172. Licensed CC0.

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