{"doi":"10.3389/fimmu.2021.729837","title":"Dual-Antigen COVID-19 Vaccine Subcutaneous Prime Delivery With Oral Boosts Protects NHP Against SARS-CoV-2 Challenge","abstract":"We have developed a dual-antigen COVID-19 vaccine incorporating genes for a modified SARS-CoV-2 spike protein (S-Fusion) and the viral nucleocapsid (N) protein with an Enhanced T-cell Stimulation Domain (N-ETSD) to increase the potential for MHC class II responses. The vaccine antigens are delivered by a human adenovirus serotype 5 platform, hAd5 [E1-, E2b-, E3-], previously demonstrated to be effective in the presence of Ad immunity. Vaccination of rhesus macaques with the hAd5 S-Fusion + N-ETSD vaccine by subcutaneous prime injection followed by two oral boosts elicited neutralizing anti-S IgG and T helper cell 1-biased T-cell responses to both S and N that protected the upper and lower respiratory tracts from high titer (1 x 10 6 TCID 50 ) SARS-CoV-2 challenge. Notably, viral replication was inhibited within 24 hours of challenge in both lung and nasal passages, becoming undetectable within 7 days post-challenge.","journal":"Frontiers in Immunology","year":2021,"id":169534,"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":29,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.9552,"is_data_producer":false,"deposit_databanks":null,"is_oa":true,"file_count":0,"downloads":0,"has_version_chain":false,"published_date":"2021-01-01","fair_score":null,"fair_percentile":null,"algorithm_id":"datarank_citation_only_1hop_v6","ranking_scope":"data_only","authors":[{"id":247223,"name":"Jeffrey T. Safrit","orcid":"0000-0001-7441-4423","position":1,"is_corresponding":false},{"id":700545,"name":"Mohit S. Verma","orcid":"0000-0002-6374-3333","position":2,"is_corresponding":false},{"id":700546,"name":"Adrian Rice","orcid":"0000-0001-8731-312X","position":3,"is_corresponding":false},{"id":330457,"name":"Peter A. Sieling","orcid":null,"position":4,"is_corresponding":false},{"id":330453,"name":"Lise Zakin","orcid":null,"position":5,"is_corresponding":false},{"id":701315,"name":"Annie Shin","orcid":null,"position":6,"is_corresponding":false},{"id":701316,"name":"Brett Morimoto","orcid":null,"position":7,"is_corresponding":false},{"id":261496,"name":"Helty Adisetiyo","orcid":null,"position":8,"is_corresponding":false},{"id":701317,"name":"Raymond M.H. Wong","orcid":null,"position":9,"is_corresponding":false},{"id":701318,"name":"Ashish Bezawada","orcid":null,"position":10,"is_corresponding":false},{"id":700547,"name":"Kyle Dinkins","orcid":"0000-0002-1578-5993","position":11,"is_corresponding":false},{"id":701319,"name":"Joseph P. Balint","orcid":null,"position":12,"is_corresponding":false},{"id":701320,"name":"Victor Peykov","orcid":null,"position":13,"is_corresponding":false},{"id":700548,"name":"Hermes Garbán","orcid":"0000-0001-7754-5357","position":14,"is_corresponding":false},{"id":700549,"name":"Philip L.‐F. Liu","orcid":"0000-0002-2170-5507","position":15,"is_corresponding":false},{"id":700550,"name":"Andrew Bacon","orcid":"0000-0002-9099-9158","position":16,"is_corresponding":false},{"id":701321,"name":"Pete Bone","orcid":null,"position":17,"is_corresponding":false},{"id":701322,"name":"Jeff Drew","orcid":null,"position":18,"is_corresponding":false},{"id":701323,"name":"Daniel Sanford","orcid":null,"position":19,"is_corresponding":false},{"id":700551,"name":"Patricia Spilman","orcid":"0000-0003-2626-6475","position":20,"is_corresponding":false},{"id":701324,"name":"Lennie Sender","orcid":null,"position":21,"is_corresponding":false},{"id":329581,"name":"Shahrooz Rabizadeh","orcid":"0000-0002-8609-7645","position":22,"is_corresponding":false},{"id":329582,"name":"Kayvan Niazi","orcid":"0000-0002-7098-1751","position":23,"is_corresponding":false},{"id":321139,"name":"Patrick Soon‐Shiong","orcid":"0000-0002-4682-8298","position":24,"is_corresponding":false},{"id":701314,"name":"Elizabeth Gabitzsch","orcid":null,"position":0,"is_corresponding":true}],"reference_count":71,"raw_metadata":null,"created_at":"2026-07-18T23:46:15.560174Z","pmid":"34603305","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":[]}