# Programming Durable Immune Responses To Vaccination

> **NIH NIH U01** · WASHINGTON UNIVERSITY · 2020 · $693,502

## Abstract

ABSTRACT
Influenza viruses cause up to 500,000 deaths around the globe annually. 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. Licensed seasonal influenza virus vaccines do neither – the antibody
response is of limited breadth and vaccine-induced immunity appears to be of short duration. Early work has
established that induction of hemagglutinin (HA)-specific antibodies is essential and sufficient for protection.
Despite the extensive efforts and resources that have been deployed to fight influenza over the past eight
decades, it remains a major public health threat. There are major gaps in our understanding of memory B cell
(MBC) responses to influenza virus vaccination in humans: (1) does influenza vaccination induce a GC
reaction in the draining lymph node? (2) if yes, how robust is that response in comparison to those induced by
vaccines that elicit more durable serum antibody responses? 3) are all peripheral MBCs that emerge after
vaccination GC-derived? 4) if yes, what is the phenotype of GC-derived antigen-specific B cells that are
destined to become LLPCs? 5) does influenza vaccination induces a sustained increase in the frequency of
bone marrow-resident LLPCs? 6) is there a correlation between the frequency of antigen-specific GC B cells
and the increase/maintenance in bone marrow LLPCs? Tackling these gaps will allow us to discern the cellular
components that are associated with durable antibody responses following vaccination in humans. In our
studies, we will address these outstanding questions through detailed phenotypic, functional and transcriptional
analysis of influenza vaccination-induced, HA-specific B cell responses isolated not only from the easily
accessible blood compartment, but also those isolated from the draining lymph nodes and the bone marrow
compartments. Our preliminary data show that there are at least two distinct subsets of vaccine-induced B cell
subsets that differ in the kinetics of their appearance in blood, isotype distribution, and differentiation potential.
Additionally, our transcriptional analyses reveal differential expression of key transcription factors, such as
TCF-1 that are associated broadly with isotype-switching and self-renewal capacity. Elucidating the origin and
fate of influenza vaccines-induced B cell responses is unarguably a major public health need and our findings
will potentially reveal the cellular and molecular determinants dictating not only the longevity, but also the
breadth of elicited antibody responses to influenza – and potentially other – vaccination in humans.

## Key facts

- **NIH application ID:** 9840436
- **Project number:** 5U01AI141990-02
- **Recipient organization:** WASHINGTON UNIVERSITY
- **Principal Investigator:** Ali Hassan Ellebedy
- **Activity code:** U01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $693,502
- **Award type:** 5
- **Project period:** 2018-12-18 → 2023-11-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/9840436

## Citation

> US National Institutes of Health, RePORTER application 9840436, Programming Durable Immune Responses To Vaccination (5U01AI141990-02). Retrieved via AI Analytics 2026-05-22 from https://api.ai-analytics.org/grant/nih/9840436. Licensed CC0.

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