# Understanding Early-life Influenza Antibody Repertoire Imprinting Through Infection or Vaccination

> **NIH NIH P20** · DARTMOUTH COLLEGE · 2020 · $274,177

## Abstract

Influenza is a persisting global threat, and the most pressing unmet need is to improve vaccination 
strategies to be more effective, with this fundamentally hinging on a better understanding of vaccinemediated 
immunity in humans. Due to the ubiquitous nature of influenza, people are exposed to influenza 
virus at an early age, resulting in the early development of antibody responses to the first encountered 
influenza strains. From this initial exposure to influenza via infection or vaccination, the initial influenza 
antibody repertoire is established, and it is constantly reshaped during one’s lifetime. Recent studies have 
suggested that this initial antibody repertoire generated from the first exposure is ‘imprinted’ in the immune 
system and exerts a major influence on the nature of the antibody response elicited upon subsequent 
challenges. Such imprinting sets the immune system on a path that bias immune responses to subsequent 
exposures to influenza, and there is an increasing understanding that early childhood imprinting might be 
the reason for the limited effectiveness of the annual flu vaccination. This study aims to characterize the 
immune response to influenza in young children and its effect on subsequent responses to influenza 
vaccination. The hypothesis is that that the first exposure through infection results in stronger imprinting of 
initial influenza antibody repertoire than the first exposure through vaccination. In Aim 1, the immune 
response to influenza vaccine in children who had documented prior natural infection or documented prior 
vaccination will be compared, focusing on the persistence of the antibodies from the first time point over 2 
years of subsequent vaccinations. In Aim 2, the antibodies comprising the imprinted antibody repertoire will 
be functionally characterized to better understand the features of the imprinted antibodies. Collectively, this 
study will potentially elucidate the rules and mechanisms governing imprinting, which can be leveraged into 
the development of better vaccine immunogens as well as vaccination strategies.

## Key facts

- **NIH application ID:** 10215742
- **Project number:** 5P20GM113132-05
- **Recipient organization:** DARTMOUTH COLLEGE
- **Principal Investigator:** Jiwon Lee
- **Activity code:** P20 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $274,177
- **Award type:** 5
- **Project period:** 2019-07-01 → 2021-07-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10215742

## Citation

> US National Institutes of Health, RePORTER application 10215742, Understanding Early-life Influenza Antibody Repertoire Imprinting Through Infection or Vaccination (5P20GM113132-05). Retrieved via AI Analytics 2026-05-26 from https://api.ai-analytics.org/grant/nih/10215742. Licensed CC0.

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