# Impact of the Initial Influenza Exposure on the Quality, Magnitude, Breadth, Potency and Durability of Influenza Immunity

> **NIH NIH U01** · CINCINNATI CHILDRENS HOSP MED CTR · 2020 · $4,386,974

## Abstract

PROJECT SUMMARY ABSTRACT
A more universal vaccine against influenza virus infection is urgently needed. However, a major obstacle
limiting more effective and durable vaccines against influenza infection stem from the rapidly shifting nature of
viral immune dominant epitopes. Further confounding this obstacle are functional differences in the
immunological responsiveness to vaccination and susceptibility of individuals to natural infection primed by
prior exposure to influenza antigens. This type of immunological imprinting likely explains the wide discordance
in effectiveness of current seasonal influenza vaccines. Considering the near ubiquitous exposure of
individuals to influenza virus, together with the wide variability in clinical symptoms from asymptomatic to
severe infection and increasingly widespread use of seasonal immunization, immunological imprinting to
influenza virus is likely initiated during infancy with the first exposure to natural infection or immunization.
Importantly, critical knowledge gaps remain regarding how individuals respond to primary influenza exposure in
early life, in the context of natural infection or vaccination, and how a lack of pre-existing immunity effects
within-host influenza viral diversity. It is also unclear how this first exposure to influenza impacts the
subsequent immunological responsiveness to antigenically identical, similar or discordant influenza epitopes.
For infants, the impact of vertically transferred maternal immunity, or that acquired postnatally through
breastfeeding, on the quality of ensuing influenza specific immune responses remain unclear. To fill these
knowledge gaps, ongoing recruitment of a maternal-infant cohort at Cincinnati Children’s Hospital will be
expanded, along with parallel efforts in Mexico City. Both sites have ongoing surveillance providing additional
cases of symptomatic primary infection. With the proposed enrollment of more than 2000 pregnant women, our
two-site cohort is ideally suited for the proposed studies given our established infrastructure of weekly nasal
swabs and symptom reporting, scheduled blood collection to detect asymptomatic and symptomatic influenza,
maternal and cord blood and milk sample analyses and detailed evaluations of susceptibility and
immunological responses to influenza infection and vaccination in mothers and infants. Our overall hypothesis
is that primary influenza exposure in early life impacts the magnitude, durability and breadth of immunological
memory to an evolving range of influenza virus antigens and this initial imprint will have a profound effect on
subsequent influenza exposures. A team of investigators with complementary expertise in pediatric infectious
diseases, epidemiology, maternal-infant cohorts, human B and T cell immunology and influenza virology have
been assembled to address our hypothesis by investigating the immunological response of infants to primary
influenza virus natural infection compared with immunizatio...

## Key facts

- **NIH application ID:** 9925182
- **Project number:** 5U01AI144673-02
- **Recipient organization:** CINCINNATI CHILDRENS HOSP MED CTR
- **Principal Investigator:** MARY A STAAT
- **Activity code:** U01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $4,386,974
- **Award type:** 5
- **Project period:** 2019-05-15 → 2026-04-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/9925182

## Citation

> US National Institutes of Health, RePORTER application 9925182, Impact of the Initial Influenza Exposure on the Quality, Magnitude, Breadth, Potency and Durability of Influenza Immunity (5U01AI144673-02). Retrieved via AI Analytics 2026-06-11 from https://api.ai-analytics.org/grant/nih/9925182. Licensed CC0.

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