# Potentiating broadly protective local immunity to influenza virus

> **NIH NIH R21** · UNIVERSITY OF ROCHESTER · 2020 · $201,922

## Abstract

PROJECT ABSTRACT
Current influenza vaccines are primarily delivered at peripheral sites and provide systemic serological immunity
that is most commonly characterized by quantifying neutralizing antibody responses. We seek to complement
this type of immunity with lung-initiated CD4 T cell immunity. Key features of the experimental design are
vaccines that can exclusively elicit CD4 T cells and the option to incorporate linked innate activators. The
premise that underlies the strategy described here is that CD4 T cells primed through the intranasal route will
both establish resident memory cells within the lung and will foster development of memory cells that have
rapid lung-homing potential. We hypothesize that these vaccine-primed lymphocytes can be mobilized rapidly
upon natural infection and can directly provide long lasting and broadly protective immunity to future influenza
virus infections. We will further hypothesize that these virus specific CD4 T cells will facilitate the recruitment
and effector functions of other protective lymphoid cells. The goals of the work described here are thus to test
these hypotheses and dissect the characteristics of elicited anti-viral CD4 T cells elicited by priming through
the respiratory tract and evaluate the consequences for protection from influenza infection. These goals will be
accomplished through completion of three Specific Aims, utilizing experimental tools previously established in
our laboratory as well as novel strategies developed specifically for these experiments.
Specific Aim 1. Design of viral antigenic ligand constructs for elicitation of influenza-specific CD4 T
cells.
Specific Aim 2. Assay the ability of lung vaccination with nano-lipoprotein-ligands to boost the
abundance and functional potential of lung localized virus-specific CD4 T cells.
Specific Aim 3. Determine whether intranasal vaccination potentiates recruitment and/or expansion of
CD4 T cell and other effectors to the respiratory tract that protect from influenza virus infection.

## Key facts

- **NIH application ID:** 9936442
- **Project number:** 5R21AI145269-02
- **Recipient organization:** UNIVERSITY OF ROCHESTER
- **Principal Investigator:** Andrea Janine Sant
- **Activity code:** R21 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $201,922
- **Award type:** 5
- **Project period:** 2019-06-01 → 2022-05-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/9936442

## Citation

> US National Institutes of Health, RePORTER application 9936442, Potentiating broadly protective local immunity to influenza virus (5R21AI145269-02). Retrieved via AI Analytics 2026-05-25 from https://api.ai-analytics.org/grant/nih/9936442. Licensed CC0.

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