# Optimizing the generation of long-lived plasma cells

> **NIH NIH P01** · ICAHN SCHOOL OF MEDICINE AT MOUNT SINAI · 2022 · $390,000

## Abstract

Project Summary
An ideal influenza vaccine must have two essential attributes: one, it should be capable of inducing broadly
cross-reactive antibodies that can neutralize diverse influenza virus strains; and two, it must induce long-lived
antibody responses to maintain protective immunity for extended periods. The licensed inactivated influenza
virus vaccine does neither – the antibody response is of limited breadth and vaccine-induced immunity appears
to be of short duration. Our preliminary results show that the currently used seasonal inactivated trivalent
influenza vaccine (TIV) is not efficient in generating long-lived bone marrow plasma cells in humans and that
this is the cellular defect that underlies the waning immunity seen after influenza vaccination. In addition, our
recent data suggest that there is minimal somatic hypermutation in influenza-specific B cells after immunization
with TIV. This suggests that the vaccine fails to elicit the robust germinal center responses that are thought to
be required for generating long-lived plasma cells. As we move towards the goal of developing a “Universal”
influenza vaccine, there is a compelling need for a product that will provide long-lasting protection against
many different strains of influenza viruses. Previous studies have shown that some live attenuated viral
vaccines or infections are able to induce antibody responses that persist for a lifetime in humans, while
responses to protein vaccines typically decline much faster. This suggests that there are qualitative differences
in the plasma cells elicited by live versus inactivated vaccines. Our proposal addresses fundamental questions
about the generation of influenza-specific long-lived plasma cells and their persistence in the bone marrow
both in humans and in mice following vaccination or infection. The following specific aims are proposed:
Specific Aim 1; To determine the duration of humoral immunity to influenza virus infection versus vaccination in
humans; and Specific Aim 2: To optimize strategies for using adjuvants and the vaccine candidates developed
in this program project to generate long lived bone marrow plasma cells in mice. Our studies will be highly
synergistic with other projects and cores in this Program Project grant.

## Key facts

- **NIH application ID:** 10468076
- **Project number:** 5P01AI097092-10
- **Recipient organization:** ICAHN SCHOOL OF MEDICINE AT MOUNT SINAI
- **Principal Investigator:** Rafi Ahmed
- **Activity code:** P01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2022
- **Award amount:** $390,000
- **Award type:** 5
- **Project period:** 2012-08-01 → 2024-07-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10468076

## Citation

> US National Institutes of Health, RePORTER application 10468076, Optimizing the generation of long-lived plasma cells (5P01AI097092-10). Retrieved via AI Analytics 2026-05-24 from https://api.ai-analytics.org/grant/nih/10468076. Licensed CC0.

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