# Mechanisms of antibody-dependent enhancement of SARS-CoV-2 infection

> **NIH NIH R01** · ROCKEFELLER UNIVERSITY · 2020 · $141,249

## Abstract

Abstract
The ongoing COVID-19 pandemic represents a public health emergency of global concern, due to the high levels
of morbidity and mortality, as well as the ease of transmission. Intensive research efforts are currently focused
in the development of antibody-based therapeutics that would neutralize SARS-CoV-2 and provide robust
antiviral activity. In addition, several vaccine candidates are currently being tested, as an effort to provide long-
lasting immunity against SARS-CoV-2. However, a major concern about the safety of these approaches stems
from the capacity of antibodies -either administered passively or elicited upon vaccination- to enhance viral
infection, a phenomenon that is termed as antibody-dependent enhancement (ADE). Although ADE has been
primarily demonstrated for flaviviruses, like dengue, it is unknown whether this phenomenon also extends to
coronaviruses. Like dengue disease, COVID-19 patients exhibit a wide range of clinical disease severity, ranging
from asymptomatic to severe symptomatic disease, which is often fatal. This suggests that host immune factors
likely determine disease susceptibility and are critical for progression to severe disease. Additionally, SARS-
CoV-2, the causative agent for COVID-19, shares high degree of sequence similarity with other human and bat
coronaviruses, including SARS-CoV and MERS-CoV. Similar to what has been shown for dengue, it is likely that
pre-existing immunity against other coronaviruses might predispose for SARS-CoV-2 infection and development
of severe COVID-19 disease. Likewise, active or passive immunization against SARS-CoV-2 might increase the
susceptibility to infection with other coronaviruses via the presence of non-neutralizing, cross-reactive antibodies.
Although there is limited evidence on the capacity of anti-SARS-CoV-2 antibodies to mediate ADE, several prior
studies on SARS-CoV have provided some preliminary evidence that under specific conditions, anti-SARS-CoV
antibodies might enhance infection of FcγR-expressing cells. Given the ongoing clinical development efforts for
antibody-based therapeutics and vaccines to control SARS-CoV-2 infection, it is important to assess whether
anti-SARS-CoV-2 antibodies have the capacity to mediate ADE and if so, determine the precise molecular
mechanisms and the role of FcγRs in this process. Our proposed studies aim to: (i) determine the ADE activity
of IgG antibodies purified from recovered COVID-19 patients with variable degree of disease severity, (ii)
generate and evaluate the ADE activity of anti-SARS-CoV-2 and anti-SARS-CoV mAbs with variable cross-
reactivity and neutralization potency, and (iii) compare the ADE activity of Fc domain variants of these mAbs with
selectively enhanced binding to specific human FcγRs to determine the role for human FcγRs in mediating ADE
activity. We anticipate that these studies will address a significance safety concern about the capacity of
antibodies to mediate ADE of coronaviruses, acce...

## Key facts

- **NIH application ID:** 10142749
- **Project number:** 3R01AI137276-02S1
- **Recipient organization:** ROCKEFELLER UNIVERSITY
- **Principal Investigator:** Stylianos Bournazos
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $141,249
- **Award type:** 3
- **Project period:** 2020-05-18 → 2021-08-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10142749

## Citation

> US National Institutes of Health, RePORTER application 10142749, Mechanisms of antibody-dependent enhancement of SARS-CoV-2 infection (3R01AI137276-02S1). Retrieved via AI Analytics 2026-05-27 from https://api.ai-analytics.org/grant/nih/10142749. Licensed CC0.

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