{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,11]],"date-time":"2026-09-11T22:08:34Z","timestamp":1789164514440,"version":"build-2803163510"},"reference-count":48,"publisher":"MDPI AG","issue":"10","license":[{"start":{"date-parts":[[2024,10,18]],"date-time":"2024-10-18T00:00:00Z","timestamp":1729209600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"National Institutes of Health","award":["R01AI 170535-02"],"award-info":[{"award-number":["R01AI 170535-02"]}]},{"name":"National Institutes of Health","award":["R01CA 269384-02"],"award-info":[{"award-number":["R01CA 269384-02"]}]},{"name":"National Institutes of Health","award":["P50CA 210964-06"],"award-info":[{"award-number":["P50CA 210964-06"]}]},{"name":"The Richard M. Schulze Family Foundation, Fastgrants.org\/Mercatus","award":["R01AI 170535-02"],"award-info":[{"award-number":["R01AI 170535-02"]}]},{"name":"The Richard M. Schulze Family Foundation, Fastgrants.org\/Mercatus","award":["R01CA 269384-02"],"award-info":[{"award-number":["R01CA 269384-02"]}]},{"name":"The Richard M. Schulze Family Foundation, Fastgrants.org\/Mercatus","award":["P50CA 210964-06"],"award-info":[{"award-number":["P50CA 210964-06"]}]},{"name":"the Harrington Foundation COVID-19 Scholar Program, Mayo Foundation","award":["R01AI 170535-02"],"award-info":[{"award-number":["R01AI 170535-02"]}]},{"name":"the Harrington Foundation COVID-19 Scholar Program, Mayo Foundation","award":["R01CA 269384-02"],"award-info":[{"award-number":["R01CA 269384-02"]}]},{"name":"the Harrington Foundation COVID-19 Scholar Program, Mayo Foundation","award":["P50CA 210964-06"],"award-info":[{"award-number":["P50CA 210964-06"]}]},{"name":"a Minnesota Part-nership for Biotechnology and Medical Genomics Award","award":["R01AI 170535-02"],"award-info":[{"award-number":["R01AI 170535-02"]}]},{"name":"a Minnesota Part-nership for Biotechnology and Medical Genomics Award","award":["R01CA 269384-02"],"award-info":[{"award-number":["R01CA 269384-02"]}]},{"name":"a Minnesota Part-nership for Biotechnology and Medical Genomics Award","award":["P50CA 210964-06"],"award-info":[{"award-number":["P50CA 210964-06"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Vaccines"],"abstract":"<jats:p>Background: Long-lived, re-activatable immunity to SARS-CoV-2 and its emerging variants will rely on T cells recognizing conserved regions of viral proteins across strains. Heterologous prime\u2013boost regimens can elicit elevated levels of circulating CD8+ T cells that provide a reservoir of first responders upon viral infection. Although most vaccines are currently delivered intramuscularly (IM), the initial site of infection is the nasal cavity. Methods: Here, we tested the hypothesis that a heterologous prime and boost vaccine regimen delivered intranasally (IN) will generate improved immune responses locally at the site of virus infection compared to intramuscular vaccine\/booster regimens. Results: In a transgenic human ACE2 murine model, both a Spike-expressing single-cycle adenovirus (SC-Ad) and an IFN\u00df safety-enhanced replication-competent Vesicular Stomatitis Virus (VSV) platform generated anti-Spike antibody and T-cell responses that diminished with age. Although SC-Ad-Spike boosted a prime with VSV-Spike-mIFN\u00df, SC-Ad-Spike alone induced maximal levels of IgG, IgA, and CD8+ T-cell responses. Conclusions: There were significant differences in T-cell responses in spleens compared to lungs, and the intranasal boost was significantly superior to the intramuscular boost in generating sentinel immune effectors at the site of the virus encounter in the lungs. These data show that serious consideration should be given to intranasal boosting with anti-SARS-CoV-2 vaccines.<\/jats:p>","DOI":"10.3390\/vaccines12101191","type":"journal-article","created":{"date-parts":[[2024,10,18]],"date-time":"2024-10-18T06:46:52Z","timestamp":1729234012000},"page":"1191","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":5,"title":["Intranasal Prime\u2013Boost with Spike Vectors Generates Antibody and T-Cell Responses at the Site of SARS-CoV-2 Infection"],"prefix":"10.3390","volume":"12","author":[{"given":"Muriel","family":"Metko","sequence":"first","affiliation":[{"name":"Department of Molecular Medicine, Mayo Clinic, Rochester, MN 55905, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jason","family":"Tonne","sequence":"additional","affiliation":[{"name":"Department of Molecular Medicine, Mayo Clinic, Rochester, MN 55905, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alexa","family":"Veliz Rios","sequence":"additional","affiliation":[{"name":"Department of Molecular Medicine, Mayo Clinic, Rochester, MN 55905, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5005-7257","authenticated-orcid":false,"given":"Jill","family":"Thompson","sequence":"additional","affiliation":[{"name":"Department of Molecular Medicine, Mayo Clinic, Rochester, MN 55905, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Haley","family":"Mudrick","sequence":"additional","affiliation":[{"name":"Molecular Pharmacology and Experimental Therapeutics Program, Mayo Clinic, Rochester, MN 55905, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"David","family":"Masopust","sequence":"additional","affiliation":[{"name":"Department of Microbiology & Immunology, University of Minnesota Medical School, 2101 6th St. SE, Minneapolis, MN 55455, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rosa Maria","family":"Diaz","sequence":"additional","affiliation":[{"name":"Department of Molecular Medicine, Mayo Clinic, Rochester, MN 55905, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8568-5664","authenticated-orcid":false,"given":"Michael A.","family":"Barry","sequence":"additional","affiliation":[{"name":"Department of Molecular Medicine, Mayo Clinic, Rochester, MN 55905, USA"},{"name":"Department of Infectious Diseases, Mayo Clinic, Rochester, MN 55905, USA"},{"name":"Department of Immunology, Mayo Clinic, Rochester, MN 55905, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Richard G.","family":"Vile","sequence":"additional","affiliation":[{"name":"Department of Molecular Medicine, Mayo Clinic, Rochester, MN 55905, USA"},{"name":"Department of Immunology, Mayo Clinic, Rochester, MN 55905, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2024,10,18]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"eabo2202","DOI":"10.1126\/sciimmunol.abo2202","article-title":"Divergent SARS-CoV-2 Omicron-reactive T and B cell responses in COVID-19 vaccine recipients","volume":"7","author":"GeurtsvanKessel","year":"2022","journal-title":"Sci. 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