{"doi":"10.1101/2022.12.12.520032","title":"Live-attenuated pediatric parainfluenza vaccine expressing 6P-stabilized SARS-CoV-2 spike protein is protective against SARS-CoV-2 variants in hamsters","abstract":"and in hamsters. To improve its immunogenicity, we generated B/HPIV3/S-6P, expressing S further stabilized with 6 proline mutations (S-6P). Intranasal immunization of hamsters with B/HPIV3/S-6P reproducibly elicited significantly higher serum anti-S IgA/IgG titers than B/HPIV3/S-2P; hamster sera efficiently neutralized variants of concern (VoCs), including Omicron variants. B/HPIV3/S-2P and B/HPIV3/S-6P immunization protected hamsters against weight loss and lung inflammation following SARS-CoV-2 challenge with the vaccine-matched strain WA1/2020 or VoCs B.1.1.7/Alpha or B.1.351/Beta and induced near-sterilizing immunity. Three weeks post-challenge, B/HPIV3/S-2P- and B/HPIV3/S-6P-immunized hamsters exhibited a robust anamnestic serum antibody response with increased neutralizing potency to VoCs, including Omicron sublineages. B/HPIV3/S-6P primed for stronger anamnestic antibody responses after challenge with WA1/2020 than B/HPIV3/S-2P. B/HPIV3/S-6P will be evaluated as an intranasal vaccine to protect infants against both HPIV3 and SARS-CoV-2. AUTHOR SUMMARY: SARS-CoV-2 infects and causes disease in all age groups. While injectable SARS-CoV-2 vaccines are effective against severe COVID-19, they do not fully prevent SARS-CoV-2 replication and transmission. This study describes the preclinical comparison in hamsters of B/HPIV3/S-2P and B/HPIV3/S-6P, live-attenuated pediatric vector vaccine candidates expressing the \"2P\" prefusion stabilized version of the SARS-CoV-2 spike protein, or the further-stabilized \"6P\" version. B/HPIV3/S-6P induced significantly stronger anti-S serum IgA and IgG responses than B/HPIV3/S-2P. A single intranasal immunization with B/HPIV3/S-6P elicited broad systemic antibody responses in hamsters that efficiently neutralized the vaccine-matched isolate as well as variants of concern, including Omicron. B/HPIV3/S-6P immunization induced near-complete airway protection against the vaccine-matched SARS-CoV-2 isolate as well as two variants. Furthermore, following SARS-CoV-2 challenge, immunized hamsters exhibited strong anamnestic serum antibody responses. Based on these data, B/HPIV3/S-6P will be further evaluated in a phase I study.","journal":"bioRxiv (Cold Spring Harbor Laboratory)","year":2022,"id":300666,"datarank":0.20794415416798362,"base_score":1.3862943611198906,"endowment":1.3862943611198906,"self_citation_contribution":0.20794415416798362,"citation_network_contribution":0.0,"self_endowment_contribution":0.20794415416798362,"citer_contribution":0.0,"corpus_percentile":null,"corpus_rank":null,"citation_count":3,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.9522,"is_data_producer":false,"deposit_databanks":null,"is_oa":true,"file_count":0,"downloads":0,"has_version_chain":false,"published_date":"2022-01-01","fair_score":null,"fair_percentile":null,"algorithm_id":"datarank_citation_only_1hop_v6","ranking_scope":"data_only","authors":[{"id":649458,"name":"Hong-Su Park","orcid":"0000-0002-8423-2188","position":1,"is_corresponding":false},{"id":649457,"name":"Yumiko Matsuoka","orcid":"0000-0002-9227-4708","position":2,"is_corresponding":false},{"id":593615,"name":"Celia Santos","orcid":"0000-0003-2915-2879","position":3,"is_corresponding":false},{"id":346915,"name":"Lijuan Yang","orcid":"0000-0001-6388-6695","position":4,"is_corresponding":false},{"id":346916,"name":"Cindy Luongo","orcid":"0000-0002-3830-3803","position":5,"is_corresponding":false},{"id":105612,"name":"Ian N. Moore","orcid":"0000-0002-0391-6466","position":6,"is_corresponding":false},{"id":232893,"name":"Reed F. Johnson","orcid":"0000-0002-4312-0550","position":7,"is_corresponding":false},{"id":391925,"name":"Nicole L. Garza","orcid":null,"position":8,"is_corresponding":false},{"id":104484,"name":"Peng Zhang","orcid":"0000-0002-6129-567X","position":9,"is_corresponding":false},{"id":392400,"name":"Paolo Lusso","orcid":"0000-0002-2813-4081","position":10,"is_corresponding":false},{"id":254592,"name":"Sonja M. Best","orcid":"0000-0003-0206-297X","position":11,"is_corresponding":false},{"id":235602,"name":"Ursula J. Buchholz","orcid":"0000-0002-2329-3198","position":12,"is_corresponding":false},{"id":649460,"name":"Cyril Le Nouën","orcid":"0000-0002-5719-4112","position":13,"is_corresponding":false},{"id":504922,"name":"Xueqiao Liu","orcid":"0000-0001-7652-241X","position":0,"is_corresponding":true}],"reference_count":44,"raw_metadata":{"citation_network_status":"fetched"},"created_at":"2026-07-19T00:31:53.559757Z","pmid":"36561185","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":[]}