# Enhancing the antiviral memory B cell response

> **NIH NIH DP2** · WASHINGTON UNIVERSITY · 2021 · $1,417,500

## Abstract

Project Summary/Abstract:
There is an urgent need to develop new approaches to induce broadly protective immunity against rapidly
mutating viruses. The induction of protective immunity requires the development of memory lymphocytes that
can rapidly recognize and neutralize the virus upon re-infection. Virus-specific memory B cells are long-lived
cells that are critical for the establishment of protective immunity by vaccines. Memory B cells mediate
protective immunity by rapidly differentiating into antibody secreting cells upon antigen re-encounter. Memory
B cells that re-encounter antigen can also undergo further mutation of their B cell receptor to increase their
affinity for viral antigen. Induction of broadly reactive memory B cells through iterative exposure to cross-
reactive viral antigens is an emerging vaccination strategy designed to protect against rapidly mutating viruses.
However, efforts to induce broadly reactive memory B cells have been hindered by the relative inefficiency with
which memory B cells diversify their B cell receptor following antigen re-encounter. Better understanding of the
mechanisms governing memory B cell development is necessary to facilitate the design of vaccines capable of
eliciting a broadly protective memory B cell response.
Additionally, effective harnessing of memory B cells to protect against mucosal viruses requires understanding
how memory B cells develop and function in barrier tissues. Memory cells are critical for the establishment of
barrier immunity, with lung-resident memory B cells recently identified as essential to elicit a rapid and robust
local antibody response following influenza challenge. However, a lack of clarity regarding the pathways
regulating memory B cells development in barrier tissues remains a significant barrier to designing vaccines
capable of inducing tissue-resident memory B cells.
This project proposes to characterize how the tissue microenvironment shapes the development of memory B
cells following viral infection. This project will first determine how viral- and tissue-specific cues influence the
transcriptional profile of memory B cells. This proposal will then identify key transcriptional regulators of
memory B cell development in barrier tissues and investigate the mechanisms by which these regulators
function. Transcriptional regulators are essential in facilitating memory lymphocyte development and function in
barrier tissues. By revealing the developmental pathway of memory B cells in barrier tissues, this study will
provide important insight into how vaccines can overcome existing challenges in order to elicit broadly
protective immunity against mucosal viruses. The development of vaccines specifically designed to induce
tissue-resident memory B cells would mark an important paradigm shift away from traditional vaccination
approaches focused on inducing a systemic virus-specific B cell response.

## Key facts

- **NIH application ID:** 10236833
- **Project number:** 1DP2AI169978-01
- **Recipient organization:** WASHINGTON UNIVERSITY
- **Principal Investigator:** BRIAN LAIDLAW
- **Activity code:** DP2 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2021
- **Award amount:** $1,417,500
- **Award type:** 1
- **Project period:** 2021-09-22 → 2024-08-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10236833

## Citation

> US National Institutes of Health, RePORTER application 10236833, Enhancing the antiviral memory B cell response (1DP2AI169978-01). Retrieved via AI Analytics 2026-05-26 from https://api.ai-analytics.org/grant/nih/10236833. Licensed CC0.

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