{"doi":"10.1101/2020.11.30.403543","title":"Immunofocusing and enhancing autologous Tier-2 HIV-1 neutralization by displaying Env trimers on two-component protein nanoparticles","abstract":"Abstract The HIV-1 envelope glycoprotein trimer is poorly immunogenic because it is covered by a dense glycan shield. As a result, recombinant Env glycoproteins generally elicit inadequate antibody levels that neutralize clinically-relevant, neutralization-resistant (Tier-2) HIV-1 strains. Multivalent antigen presentation on nanoparticles is an established strategy to increase vaccine-driven immune responses. However, due to nanoparticle instability in vivo, the display of non-native Env structures, and the inaccessibility of many neutralizing antibody (NAb) epitopes, the effects of nanoparticle display have been modest for Env trimers. Here, we generated two-component self-assembling protein nanoparticles presenting twenty SOSIP trimers of the clade C Tier-2 genotype 16055. An immunization study in rabbits demonstrated that these nanoparticles induced 60-fold higher autologous Tier-2 NAb titers than the corresponding SOSIP trimers. Epitope mapping revealed that nanoparticle presentation focused antibody responses to an immunodominant apical epitope. Thus, these nanoparticles are a promising platform to improve the immunogenicity of Env trimers with apex-proximate NAb epitopes.","journal":"bioRxiv (Cold Spring Harbor Laboratory)","year":2020,"id":121819,"datarank":0.32540071160689776,"base_score":1.9459101490553132,"endowment":1.9459101490553132,"self_citation_contribution":0.29188652235829704,"citation_network_contribution":0.033514189248600716,"self_endowment_contribution":0.29188652235829704,"citer_contribution":0.033514189248600716,"corpus_percentile":null,"corpus_rank":null,"citation_count":6,"citer_count":2,"citers_with_citation_signal":2,"citers_with_endowment":2,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.9474,"is_data_producer":false,"deposit_databanks":null,"is_oa":true,"file_count":0,"downloads":0,"has_version_chain":false,"published_date":"2020-01-01","fair_score":null,"fair_percentile":null,"algorithm_id":"datarank_citation_only_1hop_v6","ranking_scope":"data_only","authors":[{"id":230743,"name":"Aleksandar Antanasijevic","orcid":"0000-0001-9452-8954","position":1,"is_corresponding":false},{"id":555784,"name":"Marlon de Gast","orcid":"0000-0003-3976-8183","position":2,"is_corresponding":false},{"id":105400,"name":"Joel D. Allen","orcid":"0000-0003-2547-968X","position":3,"is_corresponding":false},{"id":562555,"name":"Tom P. L. Bijl","orcid":null,"position":4,"is_corresponding":false},{"id":249509,"name":"Anila Yasmeen","orcid":"0000-0002-2386-8991","position":5,"is_corresponding":false},{"id":225380,"name":"Rashmi Ravichandran","orcid":"0000-0002-2630-7487","position":6,"is_corresponding":false},{"id":511479,"name":"Judith A. Burger","orcid":"0000-0002-7311-9921","position":7,"is_corresponding":false},{"id":230741,"name":"Gabriel Ozorowski","orcid":"0000-0002-9695-8138","position":8,"is_corresponding":false},{"id":106545,"name":"Jonathan L. Torres","orcid":"0000-0003-0137-8497","position":9,"is_corresponding":false},{"id":103753,"name":"Celia C. LaBranche","orcid":"0000-0002-6653-6655","position":10,"is_corresponding":false},{"id":103755,"name":"David C. Montefiori","orcid":"0000-0003-0856-6319","position":11,"is_corresponding":false},{"id":561992,"name":"Rajesh P. Ringe","orcid":"0000-0002-6068-4163","position":12,"is_corresponding":false},{"id":240717,"name":"Marit J. van Gils","orcid":"0000-0003-3422-8161","position":13,"is_corresponding":false},{"id":249512,"name":"John P. Moore","orcid":"0000-0002-9902-6096","position":14,"is_corresponding":false},{"id":249513,"name":"Per Johan Klasse","orcid":"0000-0001-8222-278X","position":15,"is_corresponding":false},{"id":105401,"name":"Max Crispin","orcid":"0000-0002-1072-2694","position":16,"is_corresponding":false},{"id":108915,"name":"Neil P. King","orcid":"0000-0002-2978-4692","position":17,"is_corresponding":false},{"id":230082,"name":"Andrew B. Ward","orcid":"0000-0001-7153-3769","position":18,"is_corresponding":false},{"id":240718,"name":"Rogier W. Sanders","orcid":"0000-0002-2324-8573","position":19,"is_corresponding":false},{"id":240716,"name":"Philip J. M. Brouwer","orcid":"0000-0002-2902-7739","position":0,"is_corresponding":true}],"reference_count":57,"raw_metadata":{"citation_network_status":"fetched"},"created_at":"2026-07-18T23:14:46.979435Z","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":[]}