{"doi":"10.1038/s41598-021-92403-9","title":"An affinity-matured human monoclonal antibody targeting fusion loop epitope of dengue virus with in vivo therapeutic potency","abstract":"Abstract Dengue virus (DENV), from the genus flavivirus of the family flaviviridae , causes serious health problems globally. Human monoclonal antibodies (HuMAb) can be used to elucidate the mechanisms of neutralization and antibody-dependent enhancement (ADE) of DENV infections, leading to the development of a vaccine or therapeutic antibodies. Here, we generated eight HuMAb clones from an Indonesian patient infected with DENV. These HuMAbs exhibited the typical characteristics of weak neutralizing antibodies including high cross-reactivity with other flaviviruses and targeting of the fusion loop epitope (FLE). However, one of the HuMAbs, 3G9, exhibited strong neutralization (NT 50 < 0.1 μg/ml) and possessed a high somatic hyper-mutation rate of the variable region, indicating affinity-maturation. Administration of this antibody significantly prolonged the survival of interferon-α/β/γ receptor knockout C57BL/6 mice after a lethal DENV challenge. Additionally, Fc-modified 3G9 that had lost their in vitro ADE activity showed enhanced therapeutic potency in vivo and competed strongly with an ADE-prone antibody in vitro. Taken together, the affinity-matured FLE-targeting antibody 3G9 exhibits promising features for therapeutic application including a low NT 50 value, potential for treatment of various kinds of mosquito-borne flavivirus infection, and suppression of ADE. This study demonstrates the therapeutic potency of affinity-matured FLE-targeting antibodies.","journal":"Scientific Reports","year":2021,"id":159651,"datarank":0.0,"base_score":0.0,"endowment":0.0,"self_citation_contribution":0.0,"citation_network_contribution":0.0,"self_endowment_contribution":0.0,"citer_contribution":0.0,"corpus_percentile":null,"corpus_rank":null,"citation_count":40,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.9525,"is_data_producer":false,"deposit_databanks":null,"is_oa":true,"file_count":0,"downloads":0,"has_version_chain":false,"published_date":"2021-01-01","fair_score":null,"fair_percentile":null,"algorithm_id":"datarank_citation_only_1hop_v6","ranking_scope":"data_only","authors":[{"id":670944,"name":"Takeshi Kurosu","orcid":"0000-0002-4648-6419","position":1,"is_corresponding":false},{"id":290885,"name":"Ariadna Grinyo i Escuer","orcid":"0000-0003-0185-2734","position":2,"is_corresponding":false},{"id":283937,"name":"Edgar Davidson","orcid":"0000-0002-3333-2314","position":3,"is_corresponding":false},{"id":671663,"name":"Siti Churrotin","orcid":null,"position":4,"is_corresponding":false},{"id":670945,"name":"Tamaki Okabayashi","orcid":"0000-0001-8614-6593","position":5,"is_corresponding":false},{"id":671664,"name":"Orapim Puiprom","orcid":null,"position":6,"is_corresponding":false},{"id":670946,"name":"Kris Cahyo Mulyatno","orcid":"0000-0001-8926-3031","position":7,"is_corresponding":false},{"id":670947,"name":"Teguh Hari Sucipto","orcid":"0000-0003-0512-2990","position":8,"is_corresponding":false},{"id":283938,"name":"Benjamin J. Doranz","orcid":"0000-0002-8245-3083","position":9,"is_corresponding":false},{"id":670948,"name":"Kenichiro Ono","orcid":"0000-0003-1035-9765","position":10,"is_corresponding":false},{"id":670949,"name":"Soegeng Soegijanto","orcid":"0000-0002-9470-8223","position":11,"is_corresponding":false},{"id":114845,"name":"Masanori Kameoka","orcid":"0000-0001-5525-9915","position":12,"is_corresponding":false},{"id":670943,"name":"Tomohiro Kotaki","orcid":"0000-0003-0284-8278","position":0,"is_corresponding":true}],"reference_count":79,"raw_metadata":null,"created_at":"2026-07-18T23:44:39.550981Z","pmid":"34155267","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":[]}