# Dynamics of the protective vaccine-induced human influenza neuraminidase B cell response

> **NIH NIH R01** · UNIVERSITY OF ALABAMA AT BIRMINGHAM · 2022 · $759,187

## Abstract

PROJECT SUMMARY
The human immune response against influenza is dominated by the production of hemagglutinin (HA)-specific
antibodies (Abs). The yearly mutation rate in influenza HA proteins is 1-2% leading to development of new viral
strains that are resistant to previous immunity. The other most predominant glycoprotein on the virion surface is
neuraminidase (NA). Although immunogenic, predominance of human NA-specific Abs is much lower than HA,
probably because NA expression is only one fourth the amount of HA on the virion surface. The yearly rate of
mutation of NA is about half that of HA while part of the enzymatic site remains conserved across type A (IAV)
and B (IBV) influenza viruses, making NA a potentially effective target for universal vaccine and therapeutic
human monoclonal Ab (hmAb) development. Antibody responses targeting NA have demonstrated protective
and therapeutic activity against influenza infection in animals, and in humans NA-inhibiting serum Abs have been
correlated with effective protection, reduced disease severity, and duration of viral shedding, independent of or
more strongly than HA-specific Ab responses, substantiating NA as a valuable target for the prevention and
treatment of influenza in humans. Although seasonal human inactivated influenza vaccines (IIV) contain NA, the
extent and mechanisms of action of protective human NA-specific humoral responses induced by vaccination
are poorly resolved. Our research has demonstrated that IIV in humans does induce both IAV and IBV NA-
specific B cells, and that the Ab clonal lineages they encode for include those that have broad and potent ability
to protect and treat influenza infection. Further, we have demonstrated that these protective NA-specific B cell
clonal lineages are present in long-lived bone marrow plasma cells in humans following IIV and are the likely
source for their sustained presence in circulation. We posit that NA-mediated universal humoral protection, like
HA, is dependent on B cell receptor/Ab specificity, however, to a greater extent than HA is also highly dependent
on the precise Fc/IgG subclass composition of the NA-specific Ab repertoire. Our central hypothesis is that
human IIV induces NA-specific B cell responses with broad protective potential, however, those with both the
proper specificity and anti-viral activity to confer universal protection are subdominant and sporadically induced,
hence at insufficient abundance to confer optimal protection. Through precisely defining the dynamics of those
protective human NA-specific B cell clonal lineages, including their induction, frequency, persistence, precise
specificity, and mechanisms of action, we expect to obtain insight on how to optimally stimulate them for future
human universal vaccine strategies. To that end, we propose 1) define the evolution of human NA-specific B cell
clonal lineages in response to seasonal IIV 2) assess the ability of IIV-induced human NA B cell lineages to
inhibit in...

## Key facts

- **NIH application ID:** 10468065
- **Project number:** 5R01AI145332-04
- **Recipient organization:** UNIVERSITY OF ALABAMA AT BIRMINGHAM
- **Principal Investigator:** James J Kobie
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2022
- **Award amount:** $759,187
- **Award type:** 5
- **Project period:** 2019-09-16 → 2025-08-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10468065

## Citation

> US National Institutes of Health, RePORTER application 10468065, Dynamics of the protective vaccine-induced human influenza neuraminidase B cell response (5R01AI145332-04). Retrieved via AI Analytics 2026-05-26 from https://api.ai-analytics.org/grant/nih/10468065. Licensed CC0.

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