# Principal Project

> **NIH NIH U19** · EMORY UNIVERSITY · 2020 · $525,608

## Abstract

The COVID19 pandemic illustrates the urgent need for understanding human B cell responses to emergent
pathogens and its application to assessing herd immunity. Our laboratories have described the phenotypic,
immunological and molecular features of different arms of human B cell responses and in particular, the original
characterization of the human extrafollicular effector B cell activation pathway and its contribution to different
memory and plasma cells responses. On that basis, we we propose to interrogate the different arms of the B cell
response to the SARS-CoV-2 virus; to identify the B cell compartments that participate in the early, ongoing and
late post-infection responses; and to determine their contribution to the establishment of herd immunity, at least
in part through the generation of protective B cell memory. The latter is an essential feature that could be
uncoupled from the persistence of serum antibodies; and therefore, would go unrecognized unless formally
tested. We postulate that the establishment of cellular B cell memory and the ability to evaluate its magnitude
and quality will be critical to track the risk of the population to short-term re-infection and seasonal exposure; to
design vaccines capable to trigger this protective feature; and to develop SARS-CoV-2 B cell-based diagnostic
tests. These goals will be accomplished using blood samples from SARS-CoV-2-infected and convalescent
individuals through the following specific aims: Aim 1. Characterization of SARS-CoV-2-specific B cell
responses through multidimensional B cell flow cytometry A precise adjudication of the cellular origin,
magnitude, and persistence of the anti-SARS-CoV-2 B cell response will be accomplished by antigen-specific
flow cytometry and validated by multiplex antigen assays and single cell analysis of the B cell populations. Aim
2. Measurement of SARS-CoV-2-specific B cell memory and herd immunity. Phenotypic features and
antigen-specific flow cytometry assays established in aim 1, will be applied to intermediate and late post-infection
time points in order to understand: a) the cellular compartments in which SARS-CoV-2-specific B cell memory
resides; b) its quality, magnitude and distribution within the population; c) its provenance (whether from early of
late cellular precursors); and d) its concordance or conversely, uncoupling from serological responses and the
generation of long-lived plasma cells (LLPC).

## Key facts

- **NIH application ID:** 10198495
- **Project number:** 3U19AI110483-07S1
- **Recipient organization:** EMORY UNIVERSITY
- **Principal Investigator:** Ignacio E. Sanz
- **Activity code:** U19 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $525,608
- **Award type:** 3
- **Project period:** 2020-07-06 → 2023-04-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10198495

## Citation

> US National Institutes of Health, RePORTER application 10198495, Principal Project (3U19AI110483-07S1). Retrieved via AI Analytics 2026-05-24 from https://api.ai-analytics.org/grant/nih/10198495. Licensed CC0.

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