{"doi":"10.1073/pnas.2316376121","title":"Human parainfluenza virus 3 vaccine candidates attenuated by codon-pair deoptimization are immunogenic and protective in hamsters","abstract":"Human parainfluenza virus type 3 (HPIV3) is a major pediatric respiratory pathogen lacking available vaccines or antiviral drugs. We generated live-attenuated HPIV3 vaccine candidates by codon-pair deoptimization (CPD). HPIV3 open reading frames (ORFs) encoding the nucleoprotein (N), phosphoprotein (P), matrix (M), fusion (F), hemagglutinin-neuraminidase (HN), and polymerase (L) were modified singly or in combination to generate 12 viruses designated Min-N, Min-P, Min-M, Min-FHN, Min-L, Min-NP, Min-NPM, Min-NPL, Min-PM, Min-PFHN, Min-MFHN, and Min-PMFHN. CPD of N or L severely reduced growth in vitro and was not further evaluated. CPD of P or M was associated with increased and decreased interferon (IFN) response in vitro, respectively, but had little effect on virus replication. In Vero cells, CPD of F and HN delayed virus replication, but final titers were comparable to wild-type (wt) HPIV3. In human lung epithelial A549 cells, CPD F and HN induced a stronger IFN response, viral titers were reduced 100-fold, and the expression of F and HN proteins was significantly reduced without affecting N or P or the relative packaging of proteins into virions. Following intranasal infection in hamsters, replication in the nasal turbinates and lungs tended to be the most reduced for viruses bearing CPD F and HN, with maximum reductions of approximately 10-fold. Despite decreased in vivo replication (and lower expression of CPD F and HN in vitro), all viruses induced titers of serum HPIV3-neutralizing antibodies similar to wt and provided complete protection against HPIV3 challenge. In summary, CPD of HPIV3 yielded promising vaccine candidates suitable for further development.","journal":"Proceedings of the National Academy of Sciences","year":2024,"id":448766,"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":5,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.9536,"is_data_producer":false,"deposit_databanks":null,"is_oa":true,"file_count":0,"downloads":0,"has_version_chain":false,"published_date":"2024-01-01","fair_score":null,"fair_percentile":null,"algorithm_id":"datarank_citation_only_1hop_v6","ranking_scope":"data_only","authors":[{"id":731097,"name":"Sirle Saul","orcid":"0000-0001-7845-9418","position":1,"is_corresponding":false},{"id":34088,"name":"Jin Dai","orcid":"0000-0003-3063-746X","position":2,"is_corresponding":false},{"id":505706,"name":"Sonja R. Surman","orcid":null,"position":3,"is_corresponding":false},{"id":504922,"name":"Xueqiao Liu","orcid":"0000-0001-7652-241X","position":4,"is_corresponding":false},{"id":649458,"name":"Hong-Su Park","orcid":"0000-0002-8423-2188","position":5,"is_corresponding":false},{"id":649460,"name":"Cyril Le Nouën","orcid":"0000-0002-5719-4112","position":6,"is_corresponding":false},{"id":1256983,"name":"Matthias Lingemann","orcid":null,"position":7,"is_corresponding":false},{"id":439359,"name":"Bibha Dahal","orcid":"0000-0001-8746-7954","position":8,"is_corresponding":false},{"id":320718,"name":"J. Robert Coleman","orcid":"0000-0002-4062-0242","position":9,"is_corresponding":false},{"id":320713,"name":"Steffen Mueller","orcid":"0000-0003-2660-258X","position":10,"is_corresponding":false},{"id":80811,"name":"Peter L. Collins","orcid":"0000-0001-7543-7299","position":11,"is_corresponding":false},{"id":235602,"name":"Ursula J. Buchholz","orcid":"0000-0002-2329-3198","position":12,"is_corresponding":false},{"id":504924,"name":"Shirin Munir","orcid":"0000-0002-8493-0728","position":13,"is_corresponding":false},{"id":649459,"name":"Sharmin Afroz","orcid":"0000-0002-8778-3313","position":0,"is_corresponding":true}],"reference_count":49,"raw_metadata":null,"created_at":"2026-07-19T02:02:12.215092Z","pmid":"38861603","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":[]}