Definition and research guide
This page combines a MeSH definition, publication statistics and selected research abstracts. It is a starting point for reading the literature, not a medical textbook or a systematic evidence review.
Content available: 4 complete abstracts (694 words), 10 references. Full article text is not stored or reproduced here; follow the PMID, DOI or PMC links to read the original sources and their access terms.
Definition
Enhancement of viral infectivity caused by non-neutralizing antibodies. There are at least two mechanisms known to account for this: mediation by Fc receptors (receptors, FC) or by complement receptors (receptors, complement). Either the virus is complexed with antiviral immunoglobulin G and binds to Fc receptors, or virus is coated with antiviral immunoglobulin M and binds to complement receptors.
Definition: NLM Medical Subject Headings (MeSH) scope note (Public domain (U.S. National Library of Medicine); attribution requested). View the MeSH record.
Also known as: Antibody Dependent Enhancement; Antibody-Dependent Enhancements; Enhancement, Antibody-Dependent.
Where it fits in the MeSH classification
- Broader topics
- Virus Physiological Phenomena; Immune System Phenomena
Related concepts
- Receptors
- Complement
- Immunoglobulin
Research landscape
PubMed indexes 543 records tagged with the MeSH heading “Antibody-Dependent Enhancement” (counts retrieved 2026-10-29). 261 of them (48.1%) were published from 2020 onward, and the busiest period so far is 2020 onward with 261 records.
Reviews account for 137 records (25.2%) and meta-analyses for 2. Randomized controlled trials number 0 (0.0%) as a share of all records on the topic. Randomized trials make up only a small share of this literature, so much of what is known comes from laboratory, observational or descriptive work.
Show the data
| Period | Records |
|---|---|
| through 1999 | 4 |
| 2000-2009 | 73 |
| 2010-2019 | 205 |
| 2020 onward | 261 |
Publication-type chart data
| Type | Records | Share |
|---|---|---|
| Reviews | 137 | 25.2% |
| Meta-analyses | 2 | 0.4% |
| Randomized controlled trials | 0 | 0.0% |
Method: PubMed query "Antibody-Dependent Enhancement"[MeSH Terms] with publication-type and date filters, retrieved 2026-10-29.
Reading the evidence in immunology
Immune responses are studied in model organisms, in cells from donors and in patients, and the same pathway can behave differently across these settings. Mouse immune systems differ from human ones in important ways, and blood measurements may not reflect what happens in tissues. Clinical conclusions about immune-mediated disease or immunotherapy come mainly from controlled trials and long-term cohorts. Check the species and tissue studied, whether markers were linked to outcomes patients notice, and the follow-up time.
Evidence from open-access studies
These open-access studies come from PubMed’s best-match results for this heading (papers whose main topic it is), ranked here by citation count, with one recent addition. Each abstract is reproduced in full under its recorded open licence so that you can read the authors’ own words. They illustrate the literature; they are not a systematic summary of it. Citation counts measure attention, not reliability or clinical benefit.
| Study / authors | Year | Source label / design | Europe PMC citations | Licence / source |
|---|---|---|---|---|
| Antibody-dependent enhancement of severe dengue disease in humans | 2017 | Research article Design not recorded in structured metadata | 1,034 | cc by PMID 29097492 · DOI · PMC5858873 |
| Lethal antibody enhancement of dengue disease in mice is prevented by Fc modification | 2010 | Research article Design not recorded in structured metadata | 334 | cc by PMID 20168989 · DOI · PMC2820409 |
| Zika virus pathogenesis in rhesus macaques is unaffected by pre-existing immunity to dengue virus | 2017 | Research article Design not recorded in structured metadata | 180 | cc by PMID 28643775 · DOI · PMC5490051 |
| SARS-CoV-2 antibody-dependent enhancement of infection depends on antibody binding to both ACE2 and Fc receptors | 2026 | Research article Design not recorded in structured metadata | 1 | cc by PMID 41729079 · DOI · PMC12956010 |
Antibody-dependent enhancement of severe dengue disease in humans [1]
Abstract reading summary — source excerpts
- Opening excerpt
- For dengue viruses 1 to 4 (DENV1-4), a specific range of antibody titer has been shown to enhance viral replication in vitro and severe disease in animal models.
- Closing excerpt
- These results have implications for studies of dengue pathogenesis and for vaccine development, because enhancement, not just lack of protection, is of concern.
- Interpretation limits
- Verbatim excerpts from the authors’ abstract; the closing excerpt may describe a finding, limitation or recommendation. Design, population, effect size and uncertainty have not been independently extracted or appraised. Read the complete abstract and linked paper before interpreting the findings.
Read complete abstract (129 words)
For dengue viruses 1 to 4 (DENV1-4), a specific range of antibody titer has been shown to enhance viral replication in vitro and severe disease in animal models. Although suspected, such antibody-dependent enhancement of severe disease has not been shown to occur in humans. Using multiple statistical approaches to study a long-term pediatric cohort in Nicaragua, we show that risk of severe dengue disease is highest within a narrow range of preexisting anti-DENV antibody titers. By contrast, we observe protection from all symptomatic dengue disease at high antibody titers. Thus, immune correlates of severe dengue must be evaluated separately from correlates of protection against symptomatic disease. These results have implications for studies of dengue pathogenesis and for vaccine development, because enhancement, not just lack of protection, is of concern.
Abstract reproduced from the open-access article under the recorded cc by licence; © the authors. PMID 29097492 · DOI · PMC5858873
Lethal antibody enhancement of dengue disease in mice is prevented by Fc modification [2]
Abstract reading summary — source excerpts
- Opening excerpt
- Immunity to one of the four dengue virus (DV) serotypes can increase disease severity in humans upon subsequent infection with another DV serotype.
- Closing excerpt
- These observations provide insight into the pathogenesis of antibody-enhanced dengue disease and identify a novel strategy for the design of therapeutic antibodies against dengue.
- Interpretation limits
- Verbatim excerpts from the authors’ abstract; the closing excerpt may describe a finding, limitation or recommendation. Design, population, effect size and uncertainty have not been independently extracted or appraised. Read the complete abstract and linked paper before interpreting the findings.
Read complete abstract (226 words)
Immunity to one of the four dengue virus (DV) serotypes can increase disease severity in humans upon subsequent infection with another DV serotype. Serotype cross-reactive antibodies facilitate DV infection of myeloid cells in vitro by promoting virus entry via Fcgamma receptors (FcgammaR), a process known as antibody-dependent enhancement (ADE). However, despite decades of investigation, no in vivo model for antibody enhancement of dengue disease severity has been described. Analogous to human infants who receive anti-DV antibodies by transplacental transfer and develop severe dengue disease during primary infection, we show here that passive administration of anti-DV antibodies is sufficient to enhance DV infection and disease in mice using both mouse-adapted and clinical DV isolates. Antibody-enhanced lethal disease featured many of the hallmarks of severe dengue disease in humans, including thrombocytopenia, vascular leakage, elevated serum cytokine levels, and increased systemic viral burden in serum and tissue phagocytes. Passive transfer of a high dose of serotype-specific antibodies eliminated viremia, but lower doses of these antibodies or cross-reactive polyclonal or monoclonal antibodies all enhanced disease in vivo even when antibody levels were neutralizing in vitro. In contrast, a genetically engineered antibody variant (E60-N297Q) that cannot bind FcgammaR exhibited prophylactic and therapeutic efficacy against ADE-induced lethal challenge. These observations provide insight into the pathogenesis of antibody-enhanced dengue disease and identify a novel strategy for the design of therapeutic antibodies against dengue.
Abstract reproduced from the open-access article under the recorded cc by licence; © the authors. PMID 20168989 · DOI · PMC2820409
Zika virus pathogenesis in rhesus macaques is unaffected by pre-existing immunity to dengue virus [3]
Abstract reading summary — source excerpts
- Opening excerpt
- Zika virus (ZIKV) is a re-emerging virus that has recently spread into dengue virus (DENV) endemic regions and cross-reactive antibodies (Abs) could potentially affect ZIKV pathogenesis.
- Closing excerpt
- Rather our results show a reduction in the number of days of ZIKV viremia compared to naïve macaques and that the previous exposure to DENV may result in modulation of the immune response without resulting in enhancement of ZIKV pathogenesis.
- Interpretation limits
- Verbatim excerpts from the authors’ abstract; the closing excerpt may describe a finding, limitation or recommendation. Design, population, effect size and uncertainty have not been independently extracted or appraised. Read the complete abstract and linked paper before interpreting the findings.
Read complete abstract (147 words)
Zika virus (ZIKV) is a re-emerging virus that has recently spread into dengue virus (DENV) endemic regions and cross-reactive antibodies (Abs) could potentially affect ZIKV pathogenesis. Using DENV-immune serum, it has been shown in vitro that antibody-dependent enhancement (ADE) of ZIKV infection can occur. Here we study the effects of pre-existing DENV immunity on ZIKV infection in vivo. We infect two cohorts of rhesus macaques with ZIKV; one cohort has been exposed to DENV 2.8 years earlier and a second control cohort is naïve to flaviviral infection. Our results, while confirming ADE in vitro, suggest that pre-existing DENV immunity does not result in more severe ZIKV disease. Rather our results show a reduction in the number of days of ZIKV viremia compared to naïve macaques and that the previous exposure to DENV may result in modulation of the immune response without resulting in enhancement of ZIKV pathogenesis.
Abstract reproduced from the open-access article under the recorded cc by licence; © the authors. PMID 28643775 · DOI · PMC5490051
SARS-CoV-2 antibody-dependent enhancement of infection depends on antibody binding to both ACE2 and Fc receptors [4]
Abstract reading summary — source excerpts
- Opening excerpt
- Antibody-dependent enhancement (ADE) of infection is a well-described phenomenon for several viruses, including dengue, Ebola, respiratory syncytial virus, and HIV.
- Closing excerpt
- 1 (Omicron) variant revealed reduced or lost ADE for most mAbs, with increased ADE observed for several mAbs relative to the USA-WA1/2020 strain.
- Interpretation limits
- Verbatim excerpts from the authors’ abstract; the closing excerpt may describe a finding, limitation or recommendation. Design, population, effect size and uncertainty have not been independently extracted or appraised. Read the complete abstract and linked paper before interpreting the findings.
Read complete abstract (192 words)
Antibody-dependent enhancement (ADE) of infection is a well-described phenomenon for several viruses, including dengue, Ebola, respiratory syncytial virus, and HIV. ADE occurs when virus-antibody complexes engage Fc receptors (FcRs) and virus-specific receptors, enhancing infection under conditions of incomplete neutralization. The Coronavirus Immunotherapeutic Consortium (CoVIC) assembled a comprehensive dataset of functional properties for over 400 mAbs, enabling direct comparison of neutralization, Fc-mediated functions, receptor binding, and infection of immune cells. Infection rates in most primary human immune cell types were low, with modest increases observed for some mAbs. In contrast, macrophages were more susceptible to SARS-CoV-2 and exhibited substantial ADE with select mAbs. ADE was completely inhibited by FcR blockade and significantly reduced by antibody- or ceftazidime-mediated blocking of angiotensin-converting enzyme 2 (ACE2). Neutralization potency did not correlate with ADE, as both strongly and weakly neutralizing antibodies induced enhancement. Instead, ADE magnitude depended on an antibody's ability to block spike protein binding to ACE2. Importantly, ADE resulted in productive infection with release of infectious virus. Evaluation of antibodies against the BA.1 (Omicron) variant revealed reduced or lost ADE for most mAbs, with increased ADE observed for several mAbs relative to the USA-WA1/2020 strain.
Abstract reproduced from the open-access article under the recorded cc by licence; © the authors. PMID 41729079 · DOI · PMC12956010
Key reviews and meta-analyses
The most cited review-type papers among PubMed’s best-match results for this heading, listed with bibliographic details only. Follow the links for the full text and access terms.
- Research article The role of IgG Fc receptors in antibody-dependent enhancement [5]
- Research article Secondary infection as a risk factor for dengue hemorrhagic fever/dengue shock syndrome: an historical perspective and role of antibody-dependent enhancement of infection [6]
- Research article Antibody-dependent enhancement and SARS-CoV-2 vaccines and therapies [7]
- Research article Intrinsic antibody-dependent enhancement of microbial infection in macrophages: disease regulation by immune complexes [8]
- Research article Dengue Antibody-Dependent Enhancement: Knowns and Unknowns [9]
- Research article Antibody-dependent enhancement of viral infection: molecular mechanisms and in vivo implications [10]
References
- Katzelnick LC, Gresh L, Halloran ME, Mercado JC, Kuan G, Gordon A, et al.. Antibody-dependent enhancement of severe dengue disease in humans. . 2017. PMID 29097492 · DOI · PMC5858873
- Balsitis SJ, Williams KL, Lachica R, Flores D, Kyle JL, Mehlhop E, et al.. Lethal antibody enhancement of dengue disease in mice is prevented by Fc modification. . 2010. PMID 20168989 · DOI · PMC2820409
- Pantoja P, Pérez-Guzmán EX, Rodríguez IV, White LJ, González O, Serrano C, et al.. Zika virus pathogenesis in rhesus macaques is unaffected by pre-existing immunity to dengue virus. . 2017. PMID 28643775 · DOI · PMC5490051
- Kuzmina NA, Periasamy S, Kedarinath K, Hernandez K, Atyeo C, Dennison SM, et al.. SARS-CoV-2 antibody-dependent enhancement of infection depends on antibody binding to both ACE2 and Fc receptors. . 2026. PMID 41729079 · DOI · PMC12956010
- Bournazos S, Gupta A, Ravetch JV. The role of IgG Fc receptors in antibody-dependent enhancement. Nat Rev Immunol. 2020. PMID 32782358 · DOI · PMC7418887
- Guzman MG, Alvarez M, Halstead SB. Secondary infection as a risk factor for dengue hemorrhagic fever/dengue shock syndrome: an historical perspective and role of antibody-dependent enhancement of infection. Arch Virol. 2013. PMID 23471635 · DOI
- Lee WS, Wheatley AK, Kent SJ, DeKosky BJ. Antibody-dependent enhancement and SARS-CoV-2 vaccines and therapies. Nat Microbiol. 2020. PMID 32908214 · DOI · PMC12103240
- Halstead SB, Mahalingam S, Marovich MA, Ubol S, Mosser DM. Intrinsic antibody-dependent enhancement of microbial infection in macrophages: disease regulation by immune complexes. Lancet Infect Dis. 2010. PMID 20883967 · DOI · PMC3057165
- Halstead SB. Dengue Antibody-Dependent Enhancement: Knowns and Unknowns. Microbiol Spectr. 2014. PMID 26104444 · DOI
- Takada A, Kawaoka Y. Antibody-dependent enhancement of viral infection: molecular mechanisms and in vivo implications. Rev Med Virol. 2003. PMID 14625886 · DOI
About this article
- Sources
- NLM Medical Subject Headings (definition, synonyms); NCBI PubMed (counts, identifiers); Europe PMC (open-access abstracts and citation counts).
- Verification
- Every reference was resolved against PubMed on 2026-10-31; title, year and DOI matched.
- Review state
- automated source verified; no human expert review has been recorded yet.
- Version
- 1, last updated 2026-10-29.
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Evidence strength
EvidenceHelix's computed view of the study designs behind this topic: how common meta-analyses, randomized trials and reviews are, how recent the literature is, and a plain-language reading. It describes the design mix of the literature. It is not a quality appraisal of any study, and it is not medical advice.