{"doi":"10.1126/sciimmunol.adu8878","title":"Simultaneous induction of multiple classes of broadly neutralizing antibody precursors by combination germline-targeting immunization in nonhuman primates","abstract":"Inducing broadly neutralizing antibodies (bnAbs) against HIV remains a key challenge in vaccine development. Germline-targeting immunogens have effectively primed bnAb B cell lineages to individual HIV envelope epitopes in humans and nonhuman primates. However, eliciting consistent bnAb breadth requires the induction of multiple bnAb classes. We investigated whether immunization with a combination of germline-targeting immunogens could concurrently prime multiple bnAb lineages in nonhuman primates. Animals were immunized with three immunogens, targeting distinct epitopes: the V3-glycan/N332 supersite, the V2 Apex region, and the membrane-proximal external region (MPER), either individually or in combinations of two or all three. Triple combination immunization transiently reduced V2 Apex and V3-glycan responses, but by 8 weeks postboost, bnAb precursor lineages were observed to all three epitopes. Similar somatic hypermutation was observed across groups, indicative of permissive germinal center responses. These findings support combination germline-targeting immunization as a viable strategy to prime multiple bnAb lineages simultaneously.","journal":"Science Immunology","year":2025,"id":522233,"datarank":0.29188652235829704,"base_score":1.9459101490553132,"endowment":1.9459101490553132,"self_citation_contribution":0.29188652235829704,"citation_network_contribution":0.0,"self_endowment_contribution":0.29188652235829704,"citer_contribution":0.0,"corpus_percentile":null,"corpus_rank":null,"citation_count":6,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.951,"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":1375854,"name":"M. Krystal","orcid":"0000-0001-6519-2531","position":1,"is_corresponding":false},{"id":1080630,"name":"Jon M. Steichen","orcid":"0000-0002-4586-3251","position":2,"is_corresponding":false},{"id":285899,"name":"Torben Schiffner","orcid":"0000-0001-6772-8870","position":3,"is_corresponding":false},{"id":1375412,"name":"Tasha K. Altheide","orcid":null,"position":4,"is_corresponding":false},{"id":842719,"name":"Alessia Liguori","orcid":"0000-0002-8606-574X","position":5,"is_corresponding":false},{"id":1364752,"name":"Danny Lu","orcid":"0000-0002-2340-3377","position":6,"is_corresponding":false},{"id":807723,"name":"Michael Kubitz","orcid":"0000-0002-3917-453X","position":7,"is_corresponding":false},{"id":318060,"name":"Erik Georgeson","orcid":"0000-0001-5137-4625","position":8,"is_corresponding":false},{"id":560982,"name":"Nicole Phelps","orcid":"0000-0001-9613-3921","position":9,"is_corresponding":false},{"id":560983,"name":"Ryan Tingle","orcid":"0000-0003-2874-7010","position":10,"is_corresponding":false},{"id":1364753,"name":"Nushin Alavi","orcid":"0000-0003-3848-6280","position":11,"is_corresponding":false},{"id":240478,"name":"Elana Ben‐Akiva","orcid":"0000-0003-1085-5902","position":12,"is_corresponding":false},{"id":1205751,"name":"Xiaoya Zhou","orcid":"0009-0001-5074-5815","position":13,"is_corresponding":false},{"id":772863,"name":"Carolyne Kifude","orcid":"0000-0002-0361-8645","position":14,"is_corresponding":false},{"id":391677,"name":"Claudia T. Flynn","orcid":null,"position":15,"is_corresponding":false},{"id":286693,"name":"Eva G. Rakasz","orcid":"0000-0001-8197-5309","position":16,"is_corresponding":false},{"id":236278,"name":"Darrell J. Irvine","orcid":"0000-0002-8637-1405","position":17,"is_corresponding":false},{"id":236279,"name":"William R. Schief","orcid":"0000-0002-1120-0150","position":18,"is_corresponding":false},{"id":103780,"name":"Shane Crotty","orcid":"0000-0002-6484-6262","position":19,"is_corresponding":false},{"id":807722,"name":"Henry J. Sutton","orcid":"0000-0002-6472-7116","position":0,"is_corresponding":true}],"reference_count":37,"raw_metadata":{"citation_network_status":"fetched"},"created_at":"2026-07-19T02:49:54.058858Z","pmid":"41105754","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":[]}