{"doi":"10.1101/2025.09.04.674340","title":"Rapid elicitation of a new class of neutralizing N332-glycan independent V3-glycan antibodies against HIV-1 in nonhuman primates","abstract":"Sequential immunization is a promising approach to elicit broadly neutralizing antibodies (bNAbs) against the HIV-1 Envelope (Env). However, available protocols are inefficient and involve multiple immunizations over long periods of time. Here, we present WIN332, a new engineered Env-immunogen that induces a new class of neutralizing N332-glycan-independent antibodies to the conserved V3-glycan epitope of Env after a single bolus immunization in nonhuman primates. WIN332 binds to precursors of canonical human N332-glycan-dependent (Type-I) V3-glycan bNAbs but also of a first-of-its-class N332-glycan-independent (Type-II) V3-glycan bNAb. A single immunization elicits neutralizing serum and monoclonal antibodies that are boosted and affinity matured with a heterologous immunogen. EMPEM analysis of serum antibodies, antibody cloning and cryo-EM analysis reveal that WIN332 elicits N332-glycan-independent antibodies with remarkable sequence and binding similarities with the most potent human type-I and type-II V3-glycan bNAbs. Thus, WIN332 is a promising vaccine candidate to streamline V3-glycan bNAb elicitation.","journal":"bioRxiv (Cold Spring Harbor Laboratory)","year":2025,"id":574543,"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":0,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.9504,"is_data_producer":false,"deposit_databanks":null,"is_oa":true,"file_count":0,"downloads":0,"has_version_chain":false,"published_date":"2025-01-01","fair_score":null,"fair_percentile":null,"algorithm_id":"datarank_citation_only_1hop_v6","ranking_scope":"data_only","authors":[{"id":816791,"name":"Jianqiu Du","orcid":null,"position":1,"is_corresponding":false},{"id":1329245,"name":"Zi Jie Lin","orcid":null,"position":2,"is_corresponding":false},{"id":1482270,"name":"Margaret Kerwin","orcid":null,"position":3,"is_corresponding":false},{"id":34878,"name":"Marta Tarquis-Medina","orcid":"0000-0002-3447-7566","position":4,"is_corresponding":false},{"id":1482271,"name":"Eduardo Urbano","orcid":null,"position":5,"is_corresponding":false},{"id":887618,"name":"Jiayan Cui","orcid":null,"position":6,"is_corresponding":false},{"id":410175,"name":"Meagan Watkins","orcid":null,"position":7,"is_corresponding":false},{"id":18590,"name":"Peng Zhao","orcid":"0000-0002-9296-5293","position":8,"is_corresponding":false},{"id":1010058,"name":"Rumi Habib","orcid":"0000-0002-2812-8263","position":9,"is_corresponding":false},{"id":1128926,"name":"Sukanya Ghosh","orcid":null,"position":10,"is_corresponding":false},{"id":1328764,"name":"Joyce Park","orcid":"0000-0003-2993-3464","position":11,"is_corresponding":false},{"id":1482272,"name":"Caroline Boroughs","orcid":null,"position":12,"is_corresponding":false},{"id":1455098,"name":"Agnes A. 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