{"doi":"10.1111/imr.13393","title":"Fc‐<scp>FcγR</scp> interactions during infections: From neutralizing antibodies to antibody‐dependent enhancement","abstract":"<jats:title>Summary</jats:title><jats:p>Advances in antibody technologies have resulted in the development of potent antibody‐based therapeutics with proven clinical efficacy against infectious diseases. Several monoclonal antibodies (mAbs), mainly against viruses such as SARS‐CoV‐2, HIV‐1, Ebola virus, influenza virus, and hepatitis B virus, are currently undergoing clinical testing or are already in use. Although these mAbs exhibit potent neutralizing activity that effectively blocks host cell infection, their antiviral activity results not only from Fab‐mediated virus neutralization, but also from the protective effector functions mediated through the interaction of their Fc domains with Fcγ receptors (FcγRs) on effector leukocytes. Fc‐FcγR interactions confer pleiotropic protective activities, including the clearance of opsonized virions and infected cells, as well as the induction of antiviral T‐cell responses. However, excessive or inappropriate activation of specific FcγR pathways can lead to disease enhancement and exacerbated pathology, as seen in the context of dengue virus infections. A comprehensive understanding of the diversity of Fc effector functions during infection has guided the development of engineered antiviral antibodies optimized for maximal effector activity, as well as the design of targeted therapeutic approaches to prevent antibody‐dependent enhancement of disease.</jats:p>","journal":"Immunological Reviews","year":2024,"id":638223,"datarank":0.4943755299006494,"base_score":3.295836866004329,"endowment":3.295836866004329,"self_citation_contribution":0.4943755299006494,"citation_network_contribution":0.0,"self_endowment_contribution":0.4943755299006494,"citer_contribution":0.0,"corpus_percentile":null,"corpus_rank":null,"citation_count":26,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":null,"is_data_producer":false,"deposit_databanks":null,"is_oa":false,"file_count":0,"downloads":0,"has_version_chain":false,"published_date":null,"fair_score":null,"fair_percentile":null,"algorithm_id":"datarank_citation_only_1hop_v6","ranking_scope":"data_only","authors":[{"id":109912,"name":"Stylianos Bournazos","orcid":"0000-0001-5466-5620","position":1,"is_corresponding":false},{"id":1053599,"name":"Julia E. Edgar","orcid":null,"position":0,"is_corresponding":false}],"reference_count":0,"raw_metadata":{"has_enrichment":true,"resolved":true,"title":"Fc‐<scp>FcγR</scp> interactions during infections: From neutralizing antibodies to antibody‐dependent enhancement","abstract":"<jats:title>Summary</jats:title><jats:p>Advances in antibody technologies have resulted in the development of potent antibody‐based therapeutics with proven clinical efficacy against infectious diseases. Several monoclonal antibodies (mAbs), mainly against viruses such as SARS‐CoV‐2, HIV‐1, Ebola virus, influenza virus, and hepatitis B virus, are currently undergoing clinical testing or are already in use. Although these mAbs exhibit potent neutralizing activity that effectively blocks host cell infection, their antiviral activity results not only from Fab‐mediated virus neutralization, but also from the protective effector functions mediated through the interaction of their Fc domains with Fcγ receptors (FcγRs) on effector leukocytes. Fc‐FcγR interactions confer pleiotropic protective activities, including the clearance of opsonized virions and infected cells, as well as the induction of antiviral T‐cell responses. However, excessive or inappropriate activation of specific FcγR pathways can lead to disease enhancement and exacerbated pathology, as seen in the context of dengue virus infections. A comprehensive understanding of the diversity of Fc effector functions during infection has guided the development of engineered antiviral antibodies optimized for maximal effector activity, as well as the design of targeted therapeutic approaches to prevent antibody‐dependent enhancement of disease.</jats:p>","is_dataset_classified":null,"base_score":3.091042453358316,"endowment":3.091042453358316,"datacite_reuse_total":0,"file_count":0,"downloads":0,"views":0,"has_version_chain":false,"is_dataset":false,"is_oa":false,"pmid":"39268652","pmcid":"PMC11659939","openalex_id":"https://openalex.org/W4402523426","authors":[],"funders":[{"funder_name":"National Institute of Allergy and Infectious Diseases","grant_id":"R01AI137276","title":null},{"funder_name":"National Institute of Allergy and Infectious Diseases","grant_id":"R01AI145870","title":null},{"funder_name":"National Institute of Allergy and Infectious Diseases","grant_id":"U19AI111825","title":null},{"funder_name":"National Cancer Institute","grant_id":"R01CA244327","title":null},{"funder_name":"National Institutes of Health","grant_id":"5U19AI111825-02","title":"Modulation of Human Dendritic Cell Development by Adjuvants and Vaccines"},{"funder_name":"National Institutes of Health","grant_id":"5R01CA244327-04","title":"Novel Transgenic Mouse Models Addressing Outstanding Translational Barriers in Antibody-Based Therapeutics"},{"funder_name":"National Institutes of Health","grant_id":"5R01AI137276-08","title":"Mechanisms of Antibody-Dependent Enhancement of Dengue Disease"},{"funder_name":"National Institutes of Health","grant_id":"3R01AI145870-02S1","title":"Evaluation of the FcgR mechanisms in the antibody-dependent enhancement of SARS-CoV-2 infection"}],"total_grants":8,"fwci":5.5308,"citation_percentile":0.9682441,"influential_citations":0,"citation_trend":[{"year":2025,"count":12},{"year":2026,"count":9}],"oa_status":"hybrid","license":"cc-by-nc-nd","oa_locations":[{"url":"https://onlinelibrary.wiley.com/doi/pdfdirect/10.1111/imr.13393","host_type":"journal"},{"url":"https://onlinelibrary.wiley.com/doi/pdfdirect/10.1111/imr.13393","host_type":"publisher"},{"url":"https://onlinelibrary.wiley.com/doi/pdf/10.1111/imr.13393","host_type":"publisher"},{"url":"https://doi.org/10.1111/imr.13393","host_type":"journal"},{"url":"https://pubmed.ncbi.nlm.nih.gov/39268652","host_type":"repository"},{"url":"https://www.ncbi.nlm.nih.gov/pmc/articles/11659939","host_type":"repository"},{"url":"https://pmc.ncbi.nlm.nih.gov/articles/PMC11659939/pdf/IMR-328-221.pdf","host_type":"repository"},{"url":"http://dx.doi.org/10.1111/imr.13393","host_type":""}],"fields_of_study":["Monoclonal and Polyclonal Antibodies Research","Glycosylation and Glycoproteins Research","Immunodeficiency and Autoimmune Disorders","0301 basic medicine","03 medical and health sciences","Animals","Humans","Antibodies, Monoclonal","Antibodies, Neutralizing","Antibodies, Viral","Antibody-Dependent Enhancement","Immunoglobulin Fc Fragments","Receptors, IgG","Virus Diseases"],"mesh_terms":["COVID-19","SARS-CoV-2","Animals","Antibodies, Monoclonal","Antibodies, Viral","Humans","Immunoglobulin Fc Fragments","Virus Diseases","Receptors, IgG","Antibody-Dependent Enhancement","Antibodies, Neutralizing"],"keywords":["Antibody","Immunology","Neutralizing antibody","Virology","Biology","Immunoglobulin Fc Fragments","Immunoglobulin G","Neutralization","IgG antibodies","Fc Effector Function","Antibody‐dependent Enhancement","Virus Diseases","Receptors, IgG","Antibodies in Pathology","Animals","Humans","Antibodies, Monoclonal","Antibodies, Viral","Antibodies, Neutralizing","Antibody-Dependent Enhancement"],"sdg_mappings":[],"linked_datasets":[],"clinical_trials":[],"software_tools":[],"database_accessions":[],"source":"live","citation_network_status":"fetched"},"created_at":"2026-08-06T20:19:08.216996Z","pmid":null,"pmcid":null,"fwci":null,"citation_percentile":null,"influential_citations":0,"oa_status":null,"license":null,"views":0,"total_file_size_bytes":0,"version_count":0,"fair_f":null,"fair_a":null,"fair_i":null,"fair_r":null,"fair_zscore":null,"fair_rationale":null,"fair_model":null,"fair_agent_version":null,"fair_fulltext_source":null,"fair_has_llm":null,"fair_computed_at":null,"clinical_trials":[],"software_tools":[],"db_accessions":[],"linked_datasets":[],"topics":[]}