{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,22]],"date-time":"2026-10-22T02:38:21Z","timestamp":1792636701702,"version":"4.5.0"},"reference-count":39,"publisher":"National Academy of Sciences","issue":"24","license":[{"start":{"date-parts":[[2022,6,9]],"date-time":"2022-06-09T00:00:00Z","timestamp":1654732800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/100006492","name":"Division of Intramural Research, National Institute of Allergy and Infectious Diseases","doi-asserted-by":"publisher","award":["1 ZIA Act AI001338 Project 01"],"award-info":[{"award-number":["1 ZIA Act AI001338 Project 01"]}],"id":[{"id":"10.13039\/100006492","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["www.pnas.org"],"crossmark-restriction":true},"short-container-title":["Proc. Natl. Acad. Sci. U.S.A."],"published-print":{"date-parts":[[2022,6,14]]},"abstract":"<jats:p>\n                    Current vaccines have greatly diminished the severity of the COVID-19 pandemic, even though they do not entirely prevent infection and transmission, likely due to insufficient immunity in the upper respiratory tract. Here, we compare intramuscular and intranasal administration of a live, replication-deficient modified vaccinia virus Ankara (MVA)\u2013based Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) spike (S) vaccine to raise protective immune responses in the K18-hACE2 mouse model. Using a recombinant MVA expressing firefly luciferase for tracking, live imaging revealed luminescence of the respiratory tract of mice within 6 h and persisting for 3 d following intranasal inoculation, whereas luminescence remained at the site of intramuscular vaccination. Intramuscular vaccination induced S-binding\u2013Immunoglobulin G (IgG) and neutralizing antibodies in the lungs, whereas intranasal vaccination also induced Immunoglobulin A (IgA) and higher levels of antigen-specific CD3\n                    <jats:sup>+<\/jats:sup>\n                    CD8\n                    <jats:sup>+<\/jats:sup>\n                    IFN-\u03b3\n                    <jats:sup>+<\/jats:sup>\n                    T cells. Similarly, IgG and neutralizing antibodies were present in the blood of mice immunized intranasally and intramuscularly, but IgA was detected only after intranasal inoculation. Intranasal boosting increased IgA after intranasal or intramuscular priming. While intramuscular vaccination prevented morbidity and cleared SARS-CoV-2 from the respiratory tract within several days after challenge, intranasal vaccination was more effective as neither infectious virus nor viral messenger (m)RNAs were detected in the nasal turbinates or lungs as early as 2 d after challenge, indicating prevention or rapid elimination of SARS-CoV-2 infection. Additionally, we determined that neutralizing antibody persisted for more than 6 mo and that serum induced to the Wuhan S protein neutralized pseudoviruses expressing the S proteins of variants, although with less potency, particularly for Beta and Omicron.\n                  <\/jats:p>","DOI":"10.1073\/pnas.2202069119","type":"journal-article","created":{"date-parts":[[2022,6,9]],"date-time":"2022-06-09T13:44:27Z","timestamp":1654782267000},"update-policy":"https:\/\/doi.org\/10.1073\/pnas.cm10313","source":"Crossref","is-referenced-by-count":62,"title":["Intranasal inoculation of an MVA-based vaccine induces IgA and protects the respiratory tract of hACE2 mice from SARS-CoV-2 infection"],"prefix":"10.1073","volume":"119","author":[{"given":"Jeffrey L.","family":"Americo","sequence":"first","affiliation":[{"name":"Laboratory of Viral Diseases, National Institute of Allergy and Infectious Diseases, NIH, Bethesda, MD 20892"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8916-3305","authenticated-orcid":false,"given":"Catherine A.","family":"Cotter","sequence":"additional","affiliation":[{"name":"Laboratory of Viral Diseases, National Institute of Allergy and Infectious Diseases, NIH, Bethesda, MD 20892"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Patricia L.","family":"Earl","sequence":"additional","affiliation":[{"name":"Laboratory of Viral Diseases, National Institute of Allergy and Infectious Diseases, NIH, Bethesda, MD 20892"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ruikang","family":"Liu","sequence":"additional","affiliation":[{"name":"Laboratory of Viral Diseases, National Institute of Allergy and Infectious Diseases, NIH, Bethesda, MD 20892"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2154-8564","authenticated-orcid":false,"given":"Bernard","family":"Moss","sequence":"additional","affiliation":[{"name":"Laboratory of Viral Diseases, National Institute of Allergy and Infectious Diseases, NIH, Bethesda, MD 20892"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"341","published-online":{"date-parts":[[2022,6,9]]},"reference":[{"key":"e_1_3_4_1_2","doi-asserted-by":"publisher","DOI":"10.1016\/S2666-5247(20)30172-5"},{"key":"e_1_3_4_2_2","doi-asserted-by":"publisher","DOI":"10.1080\/21645515.2017.1377376"},{"key":"e_1_3_4_3_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.cell.2020.08.026"},{"key":"e_1_3_4_4_2","doi-asserted-by":"publisher","DOI":"10.1038\/s41591-020-1070-6"},{"key":"e_1_3_4_5_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.celrep.2021.109400"},{"key":"e_1_3_4_6_2","doi-asserted-by":"publisher","DOI":"10.1126\/scitranslmed.abh0755"},{"key":"e_1_3_4_7_2","doi-asserted-by":"publisher","DOI":"10.1016\/S1473-3099(21)00396-0"},{"key":"e_1_3_4_8_2","doi-asserted-by":"publisher","DOI":"10.1016\/bs.aivir.2016.07.001"},{"key":"e_1_3_4_9_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0264-410X(96)00072-2"},{"key":"e_1_3_4_10_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0264-410X(98)00010-3"},{"key":"e_1_3_4_11_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0264-410X(99)00257-1"},{"key":"e_1_3_4_12_2","doi-asserted-by":"publisher","DOI":"10.4049\/jimmunol.172.10.6209"},{"key":"e_1_3_4_13_2","doi-asserted-by":"publisher","DOI":"10.1089\/vim.2016.0090"},{"key":"e_1_3_4_14_2","doi-asserted-by":"publisher","DOI":"10.1126\/science.aad1283"},{"key":"e_1_3_4_15_2","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.2026785118"},{"key":"e_1_3_4_16_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.immuni.2021.02.001"},{"key":"e_1_3_4_17_2","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.2026207118"},{"key":"e_1_3_4_18_2","doi-asserted-by":"publisher","DOI":"10.1128\/JVI.02260-20"},{"key":"e_1_3_4_19_2","doi-asserted-by":"publisher","DOI":"10.3390\/vaccines9010013"},{"key":"e_1_3_4_20_2","doi-asserted-by":"publisher","DOI":"10.1128\/mBio.00790-17"},{"key":"e_1_3_4_21_2","doi-asserted-by":"publisher","DOI":"10.1038\/mi.2016.28"},{"key":"e_1_3_4_22_2","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMc2103916"},{"key":"e_1_3_4_23_2","doi-asserted-by":"publisher","DOI":"10.1016\/0378-1119(91)90270-L"},{"key":"e_1_3_4_24_2","doi-asserted-by":"publisher","DOI":"10.1038\/s41590-018-0260-6"},{"key":"e_1_3_4_25_2","doi-asserted-by":"publisher","DOI":"10.1126\/sciimmunol.abj5129"},{"key":"e_1_3_4_26_2","doi-asserted-by":"publisher","DOI":"10.1126\/scitranslmed.abf1555"},{"key":"e_1_3_4_27_2","doi-asserted-by":"publisher","DOI":"10.1126\/scitranslmed.abd2223"},{"key":"e_1_3_4_28_2","doi-asserted-by":"publisher","DOI":"10.3892\/mmr.2021.12217"},{"key":"e_1_3_4_29_2","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0249499"},{"key":"e_1_3_4_30_2","doi-asserted-by":"publisher","DOI":"10.1038\/s41586-021-03324-6"},{"key":"e_1_3_4_31_2","doi-asserted-by":"publisher","DOI":"10.3389\/fimmu.2021.772240"},{"key":"e_1_3_4_32_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.celrep.2021.109452"},{"key":"e_1_3_4_33_2","doi-asserted-by":"publisher","DOI":"10.1055\/s-0028-1108143"},{"key":"e_1_3_4_34_2","doi-asserted-by":"publisher","DOI":"10.1093\/infdis\/jit105"},{"key":"e_1_3_4_35_2","doi-asserted-by":"publisher","DOI":"10.1093\/ofid\/ofv040"},{"key":"e_1_3_4_36_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.vaccine.2020.01.058"},{"key":"e_1_3_4_37_2","doi-asserted-by":"publisher","DOI":"10.1093\/infdis\/jis753"},{"key":"e_1_3_4_38_2","doi-asserted-by":"publisher","DOI":"10.1038\/s41586-020-2622-0"},{"key":"e_1_3_4_39_2","volume-title":"AVMA Guidelines for the Euthanasia of Animals: 2013 Edition","author":"American Veterinary Medical Association","year":"2013","unstructured":"American Veterinary Medical Association, AVMA Guidelines for the Euthanasia of Animals: 2013 Edition (American Veterinary Medical Association, Schaumburg, IL, 2013)."}],"container-title":["Proceedings of the National Academy of Sciences"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/pnas.org\/doi\/pdf\/10.1073\/pnas.2202069119","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2022,6,9]],"date-time":"2022-06-09T13:45:37Z","timestamp":1654782337000},"score":1,"resource":{"primary":{"URL":"https:\/\/pnas.org\/doi\/full\/10.1073\/pnas.2202069119"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2022,6,9]]},"references-count":39,"journal-issue":{"issue":"24","published-print":{"date-parts":[[2022,6,14]]}},"alternative-id":["10.1073\/pnas.2202069119"],"URL":"https:\/\/doi.org\/10.1073\/pnas.2202069119","relation":{},"ISSN":["0027-8424","1091-6490"],"issn-type":[{"value":"0027-8424","type":"print"},{"value":"1091-6490","type":"electronic"}],"subject":[],"published":{"date-parts":[[2022,6,9]]},"assertion":[{"value":"2022-02-06","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2022-04-15","order":1,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2022-06-09","order":2,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}],"article-number":"e2202069119"}}