# Defining the Fc-correlates of protection against influenza

> **NIH NIH R01** · MASSACHUSETTS GENERAL HOSPITAL · 2020 · $544,875

## Abstract

Abstract
The NIAID has named the development of a universal influenza vaccine as one if its key research
goals, and this need will not be met with traditional vaccine design. The design of a globally
protective vaccine against influenza has been hampered by the lack of a clear and definable
correlate of immunity against influenza. The current correlate of protection from influenza
infection, used to evaluate seasonal influenza vaccines, is the hemagglutination inhibition (HAI)
titer, an indirect measure of virus neutralization by antibodies. However, HAI incompletely
explains protection from seasonal influenza infection in humans. Conversely, extra-neutralizing
antibody-dependent innate immune effector functions, including antibody dependent cellular
cytotoxicity (ADCC), antibody dependent phagocytosis (ADCP), and antibody dependent
complement activation (ADC), have all been implicated in protection in mice. However, it is
uncertain whether non-neutralizing functions contribute to protection in humans. Thus, here we
aim to exploit a comprehensive, agnostic, sample-sparing humoral profiling tool - that broadly
captures Fc-profile diversity at unprecedented depths - to define the extra-neutralizing profiles
of antibodies that track with protection against influenza in humans. Two unique cohorts of well
characterized vaccinees will be profiled to define correlates of protection and correlates of the
evolution of neutralizing antibody breadth. Linked to mechanistic dissection in mice, correlates
will be dissected to define mechanistic links to guide the development of next generation vaccine
strategies aimed at inducing functional-broadly neutralizing antibodies against influenza.

## Key facts

- **NIH application ID:** 9972241
- **Project number:** 1R01AI146785-01A1
- **Recipient organization:** MASSACHUSETTS GENERAL HOSPITAL
- **Principal Investigator:** Galit Alter
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $544,875
- **Award type:** 1
- **Project period:** 2020-03-11 → 2025-02-28

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/9972241

## Citation

> US National Institutes of Health, RePORTER application 9972241, Defining the Fc-correlates of protection against influenza (1R01AI146785-01A1). Retrieved via AI Analytics 2026-05-22 from https://api.ai-analytics.org/grant/nih/9972241. Licensed CC0.

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