# Project-003

> **NIH NIH U19** · ROCKEFELLER UNIVERSITY · 2020 · $626,095

## Abstract

Abstract
Extensive research on the basic immunological mechanisms that drive human immunity has provided the general
framework by which the human immune system responds to foreign antigens. However, it is well-appreciated
that each viral infection poses unique challenges to the immune system and the elicited immune responses are
characterized by substantial heterogeneity that impacts disease susceptibility and pathogenesis, by conferring
either protective or disease-enhancing activities. The ongoing COVID-19 pandemic represents a significant
threat for global public health with tremendous socio-economic consequences. Early clinical and epidemiological
data from COVID-19 patients suggest that while for the majority of the population, SARS-CoV-2 infection causes
mild symptoms that usually resolve within a few weeks, a substantial fraction of patients develops severe, often
life-threatening, clinical complications, including acute respiratory distress syndrome and pneumonia.
Differences in the induction of protective antiviral immunity likely accounts for the differential susceptibility to
severe disease upon SARS-CoV-2 infection. Understanding the heterogeneity of immune responses elicited
upon SARS-CoV-2 infection is therefore critical for characterizing the immune mechanisms that confer protection
against COVID-19 disease, guiding the development of novel therapeutics for disease control, as well as,
determining disease susceptibility in high-risk populations. The proposed studies aim to characterize the
antibody responses that are elicited upon infection with SARS-CoV-2, determining the breadth of antibody
specificities, neutralization potency, as well as Fc domain heterogeneity of anti-SARS-CoV-2 IgG antibodies.
More specifically, we plan to recruit recovered COVID-19 patients and systematically analyze their B-cell
responses to determine their transcriptomic profile, as well as the functional properties of their B-cell receptors.
In parallel, serologic studies from these individuals aim to characterize the breadth and potency of their
neutralization activity and determine the subclass and Fc glycan distribution of anti-SARS-CoV-2 antibodies.
Additionally, Fc domain function will be assessed in well-established ADCC, ADCP, and ADE assays to evaluate
the capacity of anti-SARS-CoV-2 IgG antibodies to confer protective or pathogenic activities. Follow-up serologic
studies will be performed in a large cohort of patients with variable disease severity, ranging from asymptomatic
to severe symptomatic cases, to determine the functional activity of elicited anti-SARS-CoV-2 antibodies and
assess their Fc domain heterogeneity and effector function. These studies are within the scope of our parent
grant, as they are focused on the understanding of the immune responses that are elicited during viral infection.
We anticipate that the findings of these studies will provide novel insights into the immunological mechanisms
that confer protection or susceptibil...

## Key facts

- **NIH application ID:** 10170029
- **Project number:** 3U19AI111825-07S1
- **Recipient organization:** ROCKEFELLER UNIVERSITY
- **Principal Investigator:** JEFFREY Victor RAVETCH
- **Activity code:** U19 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $626,095
- **Award type:** 3
- **Project period:** 2020-06-05 → —

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10170029

## Citation

> US National Institutes of Health, RePORTER application 10170029, Project-003 (3U19AI111825-07S1). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/10170029. Licensed CC0.

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