ArticleJournal of virology2012
A nonfucosylated variant of the anti-HIV-1 monoclonal antibody b12 has enhanced FcγRIIIa-mediated antiviral activity in vitro but does not improve protection against mucosal SHIV challenge in macaques.
Article in Journal of virology, 2012. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 91 papers.
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The trial behind it
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Who cites it
91 citing papers in PubMed, 117 citations in OpenAlex.
- MABGEL 1: first phase 1 trial of the anti-HIV-1 monoclonal antibodies 2F5, 4E10 and 2G12 as a vaginal microbicide.PloS one · 2014Trial
- Fc Functions and Anti-HIV Neutralizing Antibodies: A Perspective.Current HIV research · 2026Article
- Harnessing innate immunity: natural killer cells and innate immune responses in reservoir clearance.Current opinion in HIV and AIDS · 2025Review
- Afucosylated broadly neutralizing antibodies targeting the HIV envelope elicit enhanced NK-cell-mediated cytotoxicity against HIV-infected CD4+ T-cell and macrophage targets.Journal of leukocyte biology · 2025Article
- Unpredicted Protective Function of Fc-Mediated Inhibitory Antibodies for HIV and SARS-CoV-2 Vaccines.The Journal of infectious diseases · 2025Review
- SIV monoclonal antibody administration spanning treatment interruption in macaques delays viral rebound and selects escape variants.Proceedings of the National Academy of Sciences of the United States of America · 2025Article
- Viral glycoprotein-mediated entry and antibody-mediated immunity in HIV-1 and SARS-CoV-2 infection.Frontiers in immunology · 2025Review
- Administration of anti-HIV-1 broadly neutralizing monoclonal antibodies with increased affinity to Fcγ receptors during acute SHIVNature communications · 2024Article
- Afucosylated broadly neutralizing antibodies enhance clearance of HIV-1 infected cells through cell-mediated killing.Communications biology · 2024Article
- Neutralizing the threat: harnessing broadly neutralizing antibodies against HIV-1 for treatment and prevention.Microbial cell (Graz, Austria) · 2024Article
- Complement contributes to antibody-mediated protection against repeated SHIV challenge.Proceedings of the National Academy of Sciences of the United States of America · 2023Article
- Antibody-dependent cellular cytotoxicity, infected cell binding and neutralization by antibodies to the SIV envelope glycoprotein.PLoS pathogens · 2023Article
- Enhancing the therapeutic activity of hyperimmune IgG against chikungunya virus using FcγRIIIa affinity chromatography.Frontiers in immunology · 2023Article
- Engaging innate immunity in HIV-1 cure strategies.Nature reviews. Immunology · 2022Review
- Antibody-mediated prevention of vaginal HIV transmission is dictated by IgG subclass in humanized mice.Science translational medicine · 2022Article
- Passive immunization of the human vagina.Human vaccines & immunotherapeutics · 2022Article
- Phagocytosis by an HIV antibody is associated with reduced viremia irrespective of enhanced complement lysis.Nature communications · 2022Article
- Vaccinal antibodies: Fc antibody engineering to improve the antiviral antibody response and induce vaccine-like effects.Human vaccines & immunotherapeutics · 2021Review
- Building a better antibody through the Fc: advances and challenges in harnessing antibody Fc effector functions for antiviral protection.Human vaccines & immunotherapeutics · 2021Review
- Cross-species higher sensitivities of FcγRIIIA/FcγRIV to afucosylated IgG for enhanced ADCC.Antibody therapeutics · 2021Article
31 more citing papers are in PubMed but not listed here.
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Authors and funding
22 authors at 12 institutions in 4 countries.
Funding
Abstract
Eliciting neutralizing antibodies is thought to be a key activity of a vaccine against human immunodeficiency virus (HIV). However, a number of studies have suggested that in addition to neutralization, interaction of IgG with Fc gamma receptors (FcγR) may play an important role in antibody-mediated protection. We have previously obtained evidence that the protective activity of the broadly neutralizing human IgG1 anti-HIV monoclonal antibody (MAb) b12 in macaques is diminished in the absence of FcγR binding capacity. To investigate antibody-dependent cellular cytotoxicity (ADCC) as a contributor to FcγR-associated protection, we developed a nonfucosylated variant of b12 (NFb12). We showed that, compared to fully fucosylated (referred to as wild-type in the text) b12, NFb12 had higher affinity for human and rhesus macaque FcγRIIIa and was more efficient in inhibiting viral replication and more effective in killing HIV-infected cells in an ADCC assay. Despite these more potent in vitro antiviral activities, NFb12 did not enhance protection in vivo against repeated low-dose vaginal challenge in the simian-human immunodeficiency virus (SHIV)/macaque model compared to wild-type b12. No difference in protection, viral load, or infection susceptibility was observed between animals given NFb12 and those given fully fucosylated b12, indicating that FcγR-mediated activities distinct from FcγRIIIa-mediated ADCC may be important in the observed protection against SHIV challenge.
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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.