A perspective on potential antibody-dependent enhancement of SARS-CoV-2
Open accessAbstract
Antibody-dependent enhancement (ADE) of disease is a general concern for the development of vaccines and antibody therapies because the mechanisms that underlie antibody protection against any virus have a theoretical potential to amplify the infection or trigger harmful immunopathology. This possibility requires careful consideration at this critical point in the pandemic of coronavirus disease 2019 (COVID-19), which is caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Here we review observations relevant to the risks of ADE of disease, and their potential implications for SARS-CoV-2 infection. At present, there are no known clinical findings, immunological assays or biomarkers that can differentiate any severe viral infection from immune-enhanced disease, whether by measuring antibodies, T cells or intrinsic host responses. In vitro systems and animal models do not predict the risk of ADE of disease, in part because protective and potentially detrimental antibody-mediated mechanisms are the same and designing animal models depends on understanding how antiviral host responses may become harmful in humans. The implications of our lack of knowledge are twofold. First, comprehensive studies are urgently needed to define clinical correlates of protective immunity against SARS-CoV-2. Second, because ADE of disease cannot be reliably predicted after either vaccination or treatment with antibodies-regardless of what virus is the causative agent-it will be essential to depend on careful analysis of safety in humans as immune interventions for COVID-19 move forward.
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Current evidence suggests SARS-CoV-2 does not productively infect macrophages, making infection enhancement unlikely.
“Current evidence indicates that SARS-CoV-2 does not productively infect macrophages, making enhancement of infection unlikely, and ADE and VAERD have so far not been demonstrated for SARS-CoV-2 (refs175,176).”
From Immunological mechanisms of vaccine-induced protection against COVID-19 in humans (2021) · cites this paper as [176]
ADE and VAERD have not yet been demonstrated for SARS-CoV-2.
“Current evidence indicates that SARS-CoV-2 does not productively infect macrophages, making enhancement of infection unlikely, and ADE and VAERD have so far not been demonstrated for SARS-CoV-2 (refs175,176).”
From Immunological mechanisms of vaccine-induced protection against COVID-19 in humans (2021) · cites this paper as [176]
There is currently no evidence supporting a role for antibody-dependent enhancement during SARS-CoV-2 infection.
“This is called antibody-dependent enhancement (ADE) of disease; however, there is currently no evidence supporting a role for ADE during SARS-CoV-2 infection152.”
From SARS-CoV-2, COVID-19 and the aging immune system (2021) · cites this paper as [152]
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“The relevance for antibody-dependent enhancement of disease (ADE) in the context of a range of different viral infections, including SARS-CoV and SARS-CoV-2, is reviewed elsewhere (Arvin et al., 2020; Bournazos et al., 2020b; Lee et al., 2020).”
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- Authors
- Arvin, A. M., Fink, K., Schmid, M. A., Cathcart, A., Spreafico, R., Havenar-Daughton, C., Lanzavecchia, A., Corti, D., & Virgin, H. W.
- Affiliations
- Stanford Medicine (US)
- Vir Biotechnology (Switzerland) (CH)
- VIR Biotechnology (United States) (US)
- Washington University in St. Louis (US)
- Corresponding author
- Arvin, Ann M.
- Virgin, Herbert W.
- ORCID
- Venue
- Nature
- Published
- 2020-07-13
- Volume
- 584
- Issue
- 7821
- Pages
- 353-363
- ISSN
- 0028-0836 (ISSN-L)
- 1476-4687
- OpenAlex
- W3040725637
- Cited by
- 485
- References
- 13
- Citations by year
- 2026: 16 · 2025: 13 · 2024: 33 · 2023: 45 · 2022: 84 · 2021: 209 · 2020: 85
- FWCI
- 13.88
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Locations
- Nature (publishedVersion)
- PubMed (publishedVersion)
- RePEc: Research Papers in Economics (submittedVersion)
- Topics
- Health Sciences › Medicine › Infectious Diseases › SARS-CoV-2 and COVID-19 Research
- Health Sciences › Medicine › Infectious Diseases › COVID-19 Clinical Research Studies
- Life Sciences › Immunology and Microbiology › Immunology › Immune responses and vaccinations
- Keywords
- antibody-dependent enhancement, SARS-CoV-2, COVID-19 pandemic, vaccine safety, antibody therapy, immunopathology, protective immunity, animal models, in vitro model
- MeSH terms
- Betacoronavirus, COVID-19, SARS-CoV-2, COVID-19 Vaccines, Animals, Antibodies, Viral, Dengue Virus, Disease Models, Animal, Humans, Immunoglobulin G, Immunoglobulin Fab Fragments, Immunoglobulin Fc Fragments, Macaca mulatta, Orthomyxoviridae, Pneumonia, Viral, Viral Vaccines, Coronavirus Infections, Antibody-Dependent Enhancement, Severe acute respiratory syndrome-related coronavirus, Mice, Rats, Antibodies, Neutralizing, HEK293 Cells, Pandemics, Middle East Respiratory Syndrome Coronavirus
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