{"doi":"10.1016/j.celrep.2021.109084","title":"Development of a VRC01-class germline targeting immunogen derived from anti-idiotypic antibodies","abstract":"An effective HIV-1 vaccine will likely need to elicit broadly neutralizing antibodies (bNAbs). Broad and potent VRC01-class bNAbs have been isolated from multiple infected individuals, suggesting that they could be reproducibly elicited by vaccination. Several HIV-1 envelope-derived germline-targeting immunogens have been designed to engage naive VRC01-class precursor B cells. However, they also present off-target epitopes that could hinder development of VRC01-class bNAbs. We characterize a panel of anti-idiotypic monoclonal antibodies (ai-mAbs) raised against inferred-germline (iGL) VRC01-class antibodies. By leveraging binding, structural, and B cell sorting data, we engineered a bispecific molecule derived from two ai-mAbs; one specific for VRC01-class heavy chains and one specific for VRC01-class light chains. The bispecific molecule preferentially activates iGL-VRC01 B cells in vitro and induces specific antibody responses in a murine adoptive transfer model with a diverse polyclonal B cell repertoire. This molecule represents an alternative non-envelope-derived germline-targeting immunogen that can selectively activate VRC01-class precursors in vivo.","journal":"Cell Reports","year":2021,"id":179396,"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":18,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.9506,"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":456705,"name":"Yu-Hsin Wan","orcid":"0000-0003-2826-9928","position":1,"is_corresponding":false},{"id":630969,"name":"Junli Feng","orcid":"0000-0002-7233-2069","position":2,"is_corresponding":false},{"id":97049,"name":"Abigail Wall","orcid":"0000-0001-8198-2138","position":3,"is_corresponding":false},{"id":585567,"name":"Safia Aljedani","orcid":"0000-0002-9078-0391","position":4,"is_corresponding":false},{"id":456703,"name":"Leah J. Homad","orcid":"0000-0001-8421-6519","position":5,"is_corresponding":false},{"id":618437,"name":"Anna J. MacCamy","orcid":"0000-0001-5552-9209","position":6,"is_corresponding":false},{"id":357029,"name":"Connor Weidle","orcid":"0000-0002-9354-2276","position":7,"is_corresponding":false},{"id":357034,"name":"Matthew D. Gray","orcid":"0000-0002-4260-9784","position":8,"is_corresponding":false},{"id":726856,"name":"Lauren Brumage","orcid":"0000-0001-9006-4750","position":9,"is_corresponding":false},{"id":414019,"name":"Justin J. Taylor","orcid":"0000-0001-9718-2901","position":10,"is_corresponding":false},{"id":254841,"name":"Marie Pancera","orcid":"0000-0001-9217-6270","position":11,"is_corresponding":false},{"id":357035,"name":"Leonidas Stamatatos","orcid":"0000-0002-1106-7097","position":12,"is_corresponding":false},{"id":97050,"name":"Andrew T. McGuire","orcid":"0000-0003-1841-6859","position":13,"is_corresponding":false},{"id":630970,"name":"Emilie Seydoux","orcid":"0000-0003-1021-4056","position":0,"is_corresponding":true}],"reference_count":92,"raw_metadata":null,"created_at":"2026-07-18T23:47:48.974996Z","pmid":"33951425","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":[]}