{"doi":"10.17615/m3c6-dq75","title":"A modified vaccinia Ankara vaccine expressing spike and nucleocapsid protects rhesus macaques against SARS-CoV-2 Delta infection","abstract":"SARS-CoV-2 vaccines should induce broadly cross-reactive humoral and T cell responses to protect against emerging variants of concern (VOCs). Here, we inactivated the furin cleavage site (FCS) of spike expressed by a modified vaccinia Ankara (MVA) virus vaccine (MVA/SdFCS) and found that FCS inactivation markedly increased spike binding to human ACE2. After vaccination of mice, the MVA/SdFCS vaccine induced eightfold higher neutralizing antibodies compared with MVA/S, which expressed spike without FCS inactivation, and protected against the Beta variant. We next added nucleocapsid to the MVA/SdFCS vaccine (MVA/SdFCS-N) and tested its immunogenicity and efficacy via intramuscular (IM), buccal (BU), or sublingual (SL) routes in rhesus macaques. IM vaccination induced spike-specific IgG in serum and mucosae (nose, throat, lung, and rectum) that neutralized the homologous (WA-1/2020) and heterologous VOCs, including Delta, with minimal loss (<2-fold) of activity. IM vaccination also induced both spike- and nucleocapsid-specific CD4 and CD8 T cell responses in the blood. In contrast, the SL and BU vaccinations induced less spike-specific IgG in secretions and lower levels of polyfunctional IgG in serum compared with IM vaccination. After challenge with the SARS-CoV-2 Delta variant, the IM route induced robust protection, the BU route induced moderate protection, and the SL route induced no protection. Vaccine-induced neutralizing and non-neutralizing antibody effector functions positively correlated with protection, but only the effector functions correlated with early protection. Thus, IM vaccination with MVA/SdFCS-N vaccine elicited cross-reactive antibody and T cell responses, protecting against heterologous SARS-CoV-2 VOC more effectively than other routes of vaccination.","journal":"UNC Libraries","year":2024,"id":499342,"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":0.9457,"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":541116,"name":"Samuel D. Stampfer","orcid":"0000-0001-7365-6754","position":1,"is_corresponding":false},{"id":218085,"name":"Katharine Floyd","orcid":"0000-0002-0866-6961","position":2,"is_corresponding":false},{"id":244973,"name":"Jennifer Wood","orcid":"0000-0001-8918-8510","position":3,"is_corresponding":false},{"id":801371,"name":"M.S. Suthar","orcid":null,"position":4,"is_corresponding":false},{"id":1347827,"name":"Amsalu Shiferaw","orcid":null,"position":5,"is_corresponding":false},{"id":244975,"name":"Rachelle L. Stammen","orcid":"0000-0002-2724-0915","position":6,"is_corresponding":false},{"id":1347828,"name":"A Schäfer","orcid":null,"position":7,"is_corresponding":false},{"id":801358,"name":"S.M. Jean","orcid":null,"position":8,"is_corresponding":false},{"id":293239,"name":"Cara Joyce","orcid":"0000-0003-0468-8271","position":9,"is_corresponding":false},{"id":1347829,"name":"S.A. Rahman","orcid":null,"position":10,"is_corresponding":false},{"id":1347361,"name":"Tamás Nagy","orcid":"0000-0001-5437-1411","position":11,"is_corresponding":false},{"id":806134,"name":"G Alter","orcid":null,"position":12,"is_corresponding":false},{"id":1347830,"name":"C J Wallace","orcid":null,"position":13,"is_corresponding":false},{"id":329379,"name":"Meredith E. Davis-Gardner","orcid":"0000-0002-6133-3613","position":14,"is_corresponding":false},{"id":1347831,"name":"M.S Parsons","orcid":null,"position":15,"is_corresponding":false},{"id":409303,"name":"Georges Khoury","orcid":"0000-0002-2136-2487","position":16,"is_corresponding":false},{"id":391460,"name":"L. Gralinski","orcid":null,"position":17,"is_corresponding":false},{"id":1347832,"name":"Sharath Gangadhara","orcid":null,"position":18,"is_corresponding":false},{"id":319338,"name":"S. Fischinger","orcid":null,"position":19,"is_corresponding":false},{"id":834941,"name":"R.R. Amara","orcid":null,"position":20,"is_corresponding":false},{"id":108364,"name":"Yannic C. Bartsch","orcid":"0000-0002-3844-3056","position":21,"is_corresponding":false},{"id":834945,"name":"N.K. Routhu","orcid":null,"position":22,"is_corresponding":false},{"id":383168,"name":"Lilin Lai","orcid":"0000-0002-9528-6990","position":23,"is_corresponding":false},{"id":253822,"name":"Pamela A. Kozlowski","orcid":"0000-0001-9906-6234","position":0,"is_corresponding":true}],"reference_count":0,"raw_metadata":null,"created_at":"2026-07-19T02:09:53.188165Z","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":[]}