ArticlePLoS pathogens2017
eCD4-Ig promotes ADCC activity of sera from HIV-1-infected patients.
Article in PLoS pathogens, 2017. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 24 papers.
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Who cites it
24 citing papers in PubMed, 30 citations in OpenAlex.
- Engineering B cells to express fully customizable antibodies with enhanced Fc functions.Nature communications · 2026Article
- mGem: Opening Env and harnessing NK cell effector functions to eliminate HIV-1-infected cells.mBio · 2026Review
- Smac mimetic combined with eCD4-Ig reverses latency without reducing SHIV reservoirs in rhesus macaques.The Journal of clinical investigation · 2026Article
- Engineering B cells to Express Fully Customizable Antibodies with Enhanced Fc Functions.Research square · 2025Article
- In vivo evolution of env in SHIV-AD8Molecular therapy : the journal of the American Society of Gene Therapy · 2025Article
- In vivo affinity maturation of the CD4 domains of an HIV-1-entry inhibitor.Nature biomedical engineering · 2024Article
- NKG2C and NKG2A coexpression defines a highly functional antiviral NK population in spontaneous HIV control.JCI insight · 2024Article
- Article
- A lentiviral vector B cell gene therapy platform for the delivery of the anti-HIV-1 eCD4-Ig-knob-in-hole-reversed immunoadhesin.Molecular therapy. Methods & clinical development · 2023Article
- Estimation of the in vivo neutralization potency of eCD4Ig and conditions for AAV-mediated production for SHIV long-term remission.Science advances · 2022Article
- Mining HIV controllers for broad and functional antibodies to recognize and eliminate HIV-infected cells.Cell reports · 2021Article
- Antibodies for Human Immunodeficiency Virus-1 Cure Strategies.The Journal of infectious diseases · 2021Review
- Opening the HIV envelope: potential of CD4 mimics as multifunctional HIV entry inhibitors.Current opinion in HIV and AIDS · 2020Review
- Engineering antibody-based molecules for HIV treatment and cure.Current opinion in HIV and AIDS · 2020Review
- Recent insights into Fc-mediated effector responses to HIV-1.Current opinion in HIV and AIDS · 2020Review
- The Conformational States of the HIV-1 Envelope Glycoproteins.Trends in microbiology · 2020Review
- Promise and Progress of an HIV-1 Cure by Adeno-Associated Virus Vector Delivery of Anti-HIV-1 Biologics.Frontiers in cellular and infection microbiology · 2020Review
- Rapid Elimination of Broadly Neutralizing Antibodies Correlates with Treatment Failure in the Acute Phase of Simian-Human Immunodeficiency Virus Infection.Journal of virology · 2019Article
- AAV-delivered eCD4-Ig protects rhesus macaques from high-dose SIVmac239 challenges.Science translational medicine · 2019Article
- eCD4-Ig Limits HIV-1 Escape More Effectively than CD4-Ig or a Broadly Neutralizing Antibody.Journal of virology · 2019Article
Corrections and comments
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Authors and funding
4 authors at 1 institution in 1 country.
Funding
Abstract
Antibody-dependent cell-mediated cytotoxity (ADCC) can eliminate HIV-1 infected cells, and may help reduce the reservoir of latent virus in infected patients. Sera of HIV-1 positive individuals include a number of antibodies that recognize epitopes usually occluded on HIV-1 envelope glycoprotein (Env) trimers. We have recently described eCD4-Ig, a potent and exceptionally broad inhibitor of HIV-1 entry that can be used to protect rhesus macaques from multiple high-dose challenges with simian-human immunodeficiency virus AD8 (SHIV-AD8). Here we show that eCD4-Ig bearing an IgG1 Fc domain (eCD4-IgG1) can mediate efficient ADCC activity against HIV-1 isolates with differing tropisms, and that it does so at least 10-fold more efficiently than CD4-Ig, even when more CD4-Ig molecules bound cell surface-expressed Env. An ADCC-inactive IgG2 form of eCD4-Ig (eCD4-IgG2) exposes V3-loop and CD4-induced epitopes on cell-expressed trimers, and renders HIV-1-infected cells susceptible to ADCC mediated by antibodies of these classes. Moreover, eCD4-IgG2, but not IgG2 forms of the broadly neutralizing antibodies VRC01 and 10-1074, enhances the ADCC activities of serum antibodies from patients by 100-fold, and significantly enhanced killing of two latently infected T-cell lines reactivated by vorinostat or TNFα. Thus eCD4-Ig is qualitatively different from CD4-Ig or neutralizing antibodies in its ability to mediate ADCC, and it may be uniquely useful in treating HIV-1 infection or reducing the reservoir of latently infected cells.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.