# DIVINCI: Dissection of Influenza Vaccination and Infection for Childhood Immunity

> **NIH NIH U01** · ST. JUDE CHILDREN'S RESEARCH HOSPITAL · 2022 · $4,901,799

## Abstract

SUMMARY
Globally, influenza virus is a major public health burden. Evidence suggests that an individual’s earliest
exposures to influenza have profound effects on immunity against the virus throughout life. Well-curated, infant
cohorts, used to interrogate the full spectrum of immune responses against early influenza exposures, and
examined for subsequent exposures have been lacking. Our premise of this proposal is that the antigenic form
(strain, infection vs. vaccination) of an encounter with influenza virus results in disparate immunological memory
profiles, particularly in B and T cell repertoires. Specifically, we will examine how influenza infection- and
vaccination-mediated imprinting modulates the breadth, longevity, and functional quality of B cell and antibody
responses and dictates the specificity, receptor profiles, functional activity and epigenetic state of the T cell
responses to subsequent influenza exposures. In addition, we will examine how these parameters are impacted
by repeated exposure to influenza. We will address these questions by comprehensively assessing the B and T
cell immune responses induced by influenza infection and vaccination in three unique birth cohort studies: 1)
Managua, Nicaragua; 2) Wellington, New Zealand; and 3) Los Angeles, CA. Through the three sites, chosen
because of our extensive experience with conduct of cohort studies and enrollment of infants, distinct seasonal
transmission of influenza, and diverse demographics, we will establish a cohort of ~3,100 children, with 2,100
newborns enrolled over the course of the U01 and an additional ~1,000 children who have already been followed
since birth for up to 8 years for symptomatic influenza infection and have existing banked blood samples. Our
central hypothesis is that the chronology of initial and subsequent influenza exposures has long lasting
effects on anti-influenza responses (“imprinting”), setting infants on diverse immunological trajectories
mediated by the recruitment of distinct B and T cell specificities and functional capabilities. We will test
this hypothesis through establishment of the cohort (Aim 1), examining the response to initial exposures (Aim 2),
examining the response to subsequent exposures (Aim 3) and evaluating correlates of protection (Aim 4). We
have formed a Consortium of world-renowned investigators who have a long history of collaboration (>150
publications). Combining extensive experience and on-going programs in clinical, immunological, and virological
research ensures a high-quality, successful research program. This U01 will result in: 1) New insight on the
mechanisms of imprinting; 2) Improved understanding of what constitutes protective immunity in early and
subsequent influenza infections, including the effects of vaccination; and 3) Identification of natural and vaccine-
induced B cell/antibody and CD4+/CD8+ T cell correlates of protection. These investigations provide a novel
opportunity to combine unique cohort...

## Key facts

- **NIH application ID:** 10400037
- **Project number:** 5U01AI144616-04
- **Recipient organization:** ST. JUDE CHILDREN'S RESEARCH HOSPITAL
- **Principal Investigator:** AUBREE L GORDON
- **Activity code:** U01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2022
- **Award amount:** $4,901,799
- **Award type:** 5
- **Project period:** 2019-05-02 → 2026-04-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10400037

## Citation

> US National Institutes of Health, RePORTER application 10400037, DIVINCI: Dissection of Influenza Vaccination and Infection for Childhood Immunity (5U01AI144616-04). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/10400037. Licensed CC0.

---

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