# Project 2

> **NIH NIH U19** · WASHINGTON UNIVERSITY · 2024 · $699,043

## Abstract

PROJECT ABSTRACT – PROJECT 2
SARS-CoV-2 and influenza A viruses are human pathogens with broad geographic range that cause pandemics
and jeopardize human health. While the rapid deployment of vaccines against COVID-19 and annual campaigns
with seasonally-matched inactivated, intramuscularly-delivered influenza vaccines have saved millions of human
lives, it has become increasingly apparent that intramuscularly-delivered vaccines do not effectively induce
mucosal immunity in the respiratory tract, which in theory, could better limit virus infection or transmission at the
portal of entry or egress. Although vaccination of antigen-naïve populations provides benefit against SARS-CoV-
2 infection, the impacts of intramuscular boosting on protection from infection by recent circulating strains has
been less impressive, in part due to the effects of immune imprinting. In Project 2 of this CCHI, we hypothesize
that viral infection in the context of prior recent vaccination induces mucosal immune responses that functionally
differ from those after infection or vaccination alone in the levels and types of cross-neutralizing and Fc effector
functions of antibodies (Abs), and cross-reactive T cell responses. Project 2 will address key knowledge gaps
as to the functional quality of infection- and vaccine-induced systemic and mucosal immunity. To achieve these
goals, we will utilize ongoing human natural history cohorts of infected and vaccinated adults with unique clinical
samples to study how vaccination impacts qualitative and quantitative systemic and mucosal antibody, B and T
cell responses, and Fc effector functions seen after SARS-CoV-2 or IAV infection. We also will utilize samples
from a unique influenza A virus human challenge cohort to assess how recent immunization with a quadrivalent
influenza vaccine (Flucelvax®) modulates induction of mucosal immunity and control of infection. Our innovative
studies on SARS-CoV-2 and influenza infection and vaccination will provide new information on human immune
responses and inform evaluation of new mucosal vaccines targeting the human respiratory tract.

## Key facts

- **NIH application ID:** 10824580
- **Project number:** 1U19AI181103-01
- **Recipient organization:** WASHINGTON UNIVERSITY
- **Principal Investigator:** Michael S Diamond
- **Activity code:** U19 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2024
- **Award amount:** $699,043
- **Award type:** 1
- **Project period:** 2024-09-04 → 2029-06-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10824580

## Citation

> US National Institutes of Health, RePORTER application 10824580, Project 2 (1U19AI181103-01). Retrieved via AI Analytics 2026-05-24 from https://api.ai-analytics.org/grant/nih/10824580. Licensed CC0.

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