# Project 3: Defining the antibody landscape after SARS-CoV-2 infection

> **NIH NIH U54** · JOHNS HOPKINS UNIVERSITY · 2022 · $432,172

## Abstract

Research Project 3 Summary
There are insufficient data regarding the long-term humoral immune responses induced after SARS-CoV-2
infection. Our preliminary data indicate that there is variation in the magnitude and duration of antibody
responses following SARS-CoV-2 infection. While IgG and IgA antibodies against spike (S) and the receptor
binding domain of S (S-RBD) appear to remain constant over time, neutralizing antibody (nAb) titers wane and
are not detected in up to 25% of infected individuals who have detectable anti-S and anti-S-RBD antibodies.
We have also observed that during the convalescent phase of SARS-CoV-2 infection, individuals with more
severe COVID-19 (i.e., hospitalized, older, and male patients) have significantly greater serological responses
to SARS-CoV-2. The antibody responses mediating protection from re-infection are not defined, and neither
are responses that may mediate greater pathology. From studies of other viruses, it is clear that a variety of
antibody functions contribute to protection from re-infection and modulate disease severity. Both nAbs and
non-nAbs can mediate a number of different activities, which include complement activation and antibody-
dependent cellular cytotoxicity (ADCC), which may contribute to pathogenesis as well as protections from
SARS-CoV-2. The overarching goal of JH-EPICS Research Project 3 is to analyze the magnitude and duration
of the total as well as functional antibody responses after SARS-CoV-2 infection. We have developed a core
set of serological assays to be applied to a prospective, demographically diverse cohort of hospitalized patients
presenting with mild, moderate, and severe COVID-19 disease. Plasma samples have and will continue to be
collected at multiple timepoints from enrollment through one year post-enrollment. Aim 1 will systematically
evaluate antibody isotype switching and the subclasses and quality of the immunoglobulins (IgG, IgM, and IgA
[monomeric and dimeric]) that recognize the SARS-CoV-2 S and S-RBD. Aim 2 will characterize the kinetics
and duration of the neutralizing antibody response against SARS-CoV-2 and the ability of viruses to escape
from nAbs. Finally, Aim 3 will analyze the function of non-neutralizing SARS-CoV-2-specific serological
response by assessing ADCC, complement-mediated cytotoxicity, and complement fixation activity toward
SARS-CoV-2 virus particles and virus-infected cells. Using linear regression analyses and modeling of these
data in the context of clinical and demographic information, we are uniquely positioned to determine the
modifiers that drive a protective antibody response following SARS-CoV-2 infection or, eventually, vaccination.

## Key facts

- **NIH application ID:** 10688368
- **Project number:** 4U54CA260492-02
- **Recipient organization:** JOHNS HOPKINS UNIVERSITY
- **Principal Investigator:** SABRA L. KLEIN
- **Activity code:** U54 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2022
- **Award amount:** $432,172
- **Award type:** 4N
- **Project period:** 2020-09-30 → 2025-08-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10688368

## Citation

> US National Institutes of Health, RePORTER application 10688368, Project 3: Defining the antibody landscape after SARS-CoV-2 infection (4U54CA260492-02). Retrieved via AI Analytics 2026-05-25 from https://api.ai-analytics.org/grant/nih/10688368. Licensed CC0.

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