# Understanding the impact of imprinted serum antibody repertoire on subsequent vaccine responses

> **NIH NIH P20** · DARTMOUTH COLLEGE · 2024 · $262,400

## Abstract

Protection against numerous infectious diseases correlates with the quantity and quality of pathogen-specific 
antibody (Ab) molecules secreted by B cells. Seasonal flu vaccines contain hemagglutinin (HA) proteins 
designed to elicit anti-HA Abs capable of conferring protective immunity against influenza infection, but the 
current annual flu vaccines confer protection only in ~60% of the population. Recent studies have focused on 
designing new HA-based immunogens that can elicit broadly-protective Abs (bpAbs) capable of protecting 
against diverse influenza strains, but bpAbs elicited by these strategies are often short-lived. A gap in our 
knowledge regarding the molecular features, functionalities, and longevity of influenza Abs, specifically related 
to the impact of pre-existing humoral memory from prior exposure, impedes the design of vaccines capable of 
generating long-lasting bpAbs. Due to the ubiquitous nature of influenza and recommended seasonal 
vaccinations, most of the population is exposed to influenza at a young age, and many studies have made 
observations that suggest Ab repertoire generated from the childhood exposure is ‘imprinted’ in the immune 
system and persists in circulation through ensuing exposures to drifted strains. Despite these observations, 
information on the clinical relevance and impact of imprinted serum Ab repertoire on subsequent vaccine 
responses is lacking. Here, we propose to apply cutting edge transcriptomic and proteomic tools to matched 
pre- and post-vaccination samples to distinguish the imprinted influenza Ab repertoire from newly elicited (de 
novo) Abs to define the biophysical and functional features of imprinted Abs. Identifying various avenues for 
overcoming potential restrictions imposed by the imprinted Ab repertoire could be key for the design of a 
universal flu vaccine that can confer long-lasting protection against diverse influenza strains.

## Key facts

- **NIH application ID:** 10904757
- **Project number:** 5P20GM113132-09
- **Recipient organization:** DARTMOUTH COLLEGE
- **Principal Investigator:** Jiwon Lee
- **Activity code:** P20 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2024
- **Award amount:** $262,400
- **Award type:** 5
- **Project period:** 2016-05-15 → 2026-05-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10904757

## Citation

> US National Institutes of Health, RePORTER application 10904757, Understanding the impact of imprinted serum antibody repertoire on subsequent vaccine responses (5P20GM113132-09). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/10904757. Licensed CC0.

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