{"doi":"10.1101/2025.05.02.651772","title":"Novel HIV-1 fusion peptide immunogens using glycan-engineered alphavirus-like particles","abstract":"Immunofocusing on conserved, subdominant epitopes is critical for vaccines against highly diverse viruses such as HIV-1, influenza, and SARS-CoV-2. The eight-residue N-terminus of the HIV-1 fusion peptide (FP) is one such example of a promising yet small target. We developed new FP immunogens using three alphavirus-like particles (VLPs) and introduced additional glycans to mask shared carrier-specific epitopes. In two independent guinea pig studies, sequential immunization with heterologous carriers enhanced FP-directed antibody titers, which were further improved with glycan engineering. Separately, using diverse FP variants sharing the same N-terminal six amino acids increased neutralizing antibody titers. When combined, these two strategies led to higher FP-directed titers and, after Env trimer boosting, induced FP-directed neutralizing antibodies against multi-clade wild-type HIV-1 in nearly all animals. These findings established the importance of minimizing recurrent off-target epitopes across immunizations and support the engineered VLPs as a promising platform for peptide immunization. Highlights: Novel HIV-1 fusion peptide immunogens using glycan-engineered alphavirus-like particlesImproved FP-directed response by minimizing recurrent carrier-specific epitopes across immunizationsImproved neutralizing response by sequential immunization with diverse FP variantsFP-directed antibodies neutralizing multi-clade wildtype viruses in nearly all animals.","journal":"bioRxiv (Cold Spring Harbor Laboratory)","year":2025,"id":565317,"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":0.9547,"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":1314441,"name":"Dedeepya R. Gudipati","orcid":null,"position":1,"is_corresponding":false},{"id":334919,"name":"Wei Shi","orcid":"0000-0002-0378-8361","position":2,"is_corresponding":false},{"id":18590,"name":"Peng Zhao","orcid":"0000-0002-9296-5293","position":3,"is_corresponding":false},{"id":481812,"name":"Winston Wu","orcid":null,"position":4,"is_corresponding":false},{"id":229153,"name":"Jeffrey C. Boyington","orcid":"0000-0003-2610-9445","position":5,"is_corresponding":false},{"id":1314023,"name":"Hardik K. Nariya","orcid":"0000-0003-3601-1927","position":6,"is_corresponding":false},{"id":1314442,"name":"Emily G. McGhee","orcid":null,"position":7,"is_corresponding":false},{"id":1036929,"name":"Tala Azzam","orcid":"0000-0001-8739-7861","position":8,"is_corresponding":false},{"id":1076058,"name":"Vedhika Raghunathan","orcid":"0000-0002-1484-0524","position":9,"is_corresponding":false},{"id":1469057,"name":"Chumeng Yang","orcid":null,"position":10,"is_corresponding":false},{"id":1277821,"name":"Catherine Yang","orcid":null,"position":11,"is_corresponding":false},{"id":425819,"name":"Christian Lee","orcid":"0000-0003-2475-9567","position":12,"is_corresponding":false},{"id":196666,"name":"J Kim","orcid":null,"position":13,"is_corresponding":false},{"id":105631,"name":"Tongqing Zhou","orcid":"0000-0002-3935-4637","position":14,"is_corresponding":false},{"id":105614,"name":"John R. Mascola","orcid":"0000-0002-5293-4695","position":15,"is_corresponding":false},{"id":227815,"name":"Lance Wells","orcid":"0000-0003-4956-5363","position":16,"is_corresponding":false},{"id":323753,"name":"Rui Kong","orcid":"0000-0003-1779-5885","position":17,"is_corresponding":false},{"id":681491,"name":"Sekyung Oh","orcid":"0000-0002-6880-5281","position":0,"is_corresponding":true}],"reference_count":67,"raw_metadata":{"citation_network_status":"fetched"},"created_at":"2026-07-19T02:56:28.709936Z","pmid":"40568149","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":[]}