{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,2]],"date-time":"2026-10-02T15:22:18Z","timestamp":1790954538667,"version":"4.1.0"},"reference-count":63,"publisher":"American Association for the Advancement of Science (AAAS)","issue":"72","content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Sci. Immunol."],"published-print":{"date-parts":[[2022,6,24]]},"abstract":"<jats:p>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 (&lt;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.<\/jats:p>","DOI":"10.1126\/sciimmunol.abo0226","type":"journal-article","created":{"date-parts":[[2022,3,31]],"date-time":"2022-03-31T17:57:25Z","timestamp":1648749445000},"source":"Crossref","is-referenced-by-count":52,"title":["A modified vaccinia Ankara vaccine expressing spike and nucleocapsid protects rhesus macaques against SARS-CoV-2 Delta infection"],"prefix":"10.1126","volume":"7","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-2080-819X","authenticated-orcid":true,"given":"Nanda Kishore","family":"Routhu","sequence":"first","affiliation":[{"name":"Division of Microbiology and Immunology, Emory Vaccine Center, Yerkes National Primate Research Center, Emory University, Atlanta, GA 30329, USA."},{"name":"Department of Microbiology and Immunology, Emory School of Medicine, Emory 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Graham SARS-CoV-2 mRNA vaccine development enabled by prototype pathogen preparedness. bioRxiv 2020.06.11.145920 [Preprint]. 11 June 2020. https:\/\/doi.org\/10.1101\/2020.06.11.145920.","DOI":"10.1101\/2020.06.11.145920"},{"key":"e_1_3_3_10_2","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMoa2101544"},{"key":"e_1_3_3_11_2","doi-asserted-by":"publisher","DOI":"10.1126\/science.abb2507"},{"key":"e_1_3_3_12_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.cell.2021.02.037"},{"key":"e_1_3_3_13_2","doi-asserted-by":"publisher","DOI":"10.1126\/science.abl9463"},{"key":"e_1_3_3_14_2","doi-asserted-by":"publisher","DOI":"10.1038\/s41586-021-03777-9"},{"key":"e_1_3_3_15_2","doi-asserted-by":"publisher","DOI":"10.1038\/s41586-021-03944-y"},{"key":"e_1_3_3_16_2","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMoa2114255"},{"key":"e_1_3_3_17_2","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMc2113468"},{"key":"e_1_3_3_18_2","doi-asserted-by":"crossref","unstructured":"M. Diamond R. 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