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One problem is intramuscular administration, which does not induce robust mucosal immune responses in the upper airways\u2014the primary site of infection and virus shedding. Here we compare the efficacy of a mucosal, replication-competent yet fully attenuated virus vaccine, sCPD9-\u0394FCS, and the monovalent mRNA vaccine BNT162b2 in preventing transmission of SARS-CoV-2 variants B.1 and Omicron BA.5 in two scenarios. Firstly, we assessed the protective efficacy of the vaccines by exposing vaccinated male Syrian hamsters to infected counterparts. Secondly, we evaluated transmission of the challenge virus from vaccinated and subsequently challenged male hamsters to na\u00efve contacts. Our findings demonstrate that the live-attenuated vaccine (LAV) sCPD9-\u0394FCS significantly outperformed the mRNA vaccine in preventing virus transmission in both scenarios. Our results provide evidence for the advantages of locally administered LAVs over intramuscularly administered mRNA vaccines in preventing infection and reducing virus transmission.<\/jats:p>","DOI":"10.1038\/s41467-024-45348-2","type":"journal-article","created":{"date-parts":[[2024,2,2]],"date-time":"2024-02-02T12:03:36Z","timestamp":1706875416000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":39,"title":["An intranasal live-attenuated SARS-CoV-2 vaccine limits virus transmission"],"prefix":"10.1038","volume":"15","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-8147-0351","authenticated-orcid":false,"given":"Julia M.","family":"Adler","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9670-5640","authenticated-orcid":false,"given":"Ricardo","family":"Martin Vidal","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7311-3477","authenticated-orcid":false,"given":"Christine","family":"Langner","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Daria","family":"Vladimirova","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Azza","family":"Abdelgawad","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Daniela","family":"Kunecova","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3361-0126","authenticated-orcid":false,"given":"Xiaoyuan","family":"Lin","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1973-3119","authenticated-orcid":false,"given":"Geraldine","family":"Nouailles","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Anne","family":"Voss","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5023-8397","authenticated-orcid":false,"given":"Sandra","family":"Kunder","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4502-0393","authenticated-orcid":false,"given":"Achim D.","family":"Gruber","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5961-2947","authenticated-orcid":false,"given":"Haibo","family":"Wu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nikolaus","family":"Osterrieder","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Dusan","family":"Kunec","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1616-0810","authenticated-orcid":false,"given":"Jakob","family":"Trimpert","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2024,2,2]]},"reference":[{"key":"45348_CR1","doi-asserted-by":"publisher","first-page":"19","DOI":"10.1001\/jama.2022.22759","volume":"329","author":"PW Marks","year":"2023","unstructured":"Marks, P. 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In this application, J.T., N.O., and D.K. are named as inventors of sCPD9. The patent application does not preclude the use of sCPD9 for scientific purposes. Freie Universit\u00e4t Berlin is collaborating with RocketVax Inc. for further development of sCPD9-\u0394FCS as a vaccine and receives funding for research. The remaining authors declare no competing interests.","order":1,"name":"Ethics","group":{"name":"EthicsHeading","label":"Competing interests"}}],"article-number":"995"}}