# Maintaining Robust T Cell Immunity For Broad Protection Against Influenza

> **NIH NIH R21** · UNIV OF MASSACHUSETTS MED SCH WORCESTER · 2020 · $209,375

## Abstract

ABSTRACT: Maintaining Robust T Cell Immunity for Broad Protection Against Influenza
Influenza vaccines currently in use are designed, primarily to produce neutralizing antibody to coat proteins and
must be reformulated and given each year. They are only partially effective, while live infection confers highly
protective T cell mediated immunity which provides multiple additional protective mechanisms and also is crucial
for generation of long-lasting neutralizing Ab.
Our recent studies indicate that generation of protective CD4 T cell immunity requires strong presentation of viral
antigen and infection-mediated signals lasting at least a week. This is because the effectors need to receive
these signals during a clear-cut checkpoint to complete their transition to memory. Current vaccines rarely supply
Ag or the relevant pathogen-recognition signals (PRS) at optimal levels for this long. Moreover, human
responses often depend on already generated memory T cells, and it is not known whether memory CD4 T cells
must go through a similar checkpoint to re-generate secondary (20) memory responses.
Here we will compare the in vivo 20 response of memory CD4 T cells generated by inactivated whole influenza
vaccine vs. live infection and determine whether the 20 CD4 effectors also need Ag and pathogen signals at a
comparable “effector checkpoint”, via similar mechanisms, to re-generate 20 CD4 memory and if such memory
does indeed provide strong heterosubtypic protection against multiple influenza A viruses.
If so, it should be possible to augment vaccines to provide the Ag and pathogen signals both initially and at the
checkpoint, and this should create a framework for a new generation of more effective vaccines against influenza
that are more broadly protective and give long-lasting immunity. Moreover, it is likely that the same strategies
could be applied to vaccines against other pathogens.

## Key facts

- **NIH application ID:** 9959343
- **Project number:** 5R21AI146532-02
- **Recipient organization:** UNIV OF MASSACHUSETTS MED SCH WORCESTER
- **Principal Investigator:** Susan L Swain
- **Activity code:** R21 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $209,375
- **Award type:** 5
- **Project period:** 2019-06-18 → 2021-05-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/9959343

## Citation

> US National Institutes of Health, RePORTER application 9959343, Maintaining Robust T Cell Immunity For Broad Protection Against Influenza (5R21AI146532-02). Retrieved via AI Analytics 2026-05-25 from https://api.ai-analytics.org/grant/nih/9959343. Licensed CC0.

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