{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,29]],"date-time":"2026-10-29T11:02:03Z","timestamp":1793271723931,"version":"4.5.0"},"reference-count":70,"publisher":"Springer Science and Business Media LLC","issue":"1","license":[{"start":{"date-parts":[[2025,7,7]],"date-time":"2025-07-07T00:00:00Z","timestamp":1751846400000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"},{"start":{"date-parts":[[2025,7,7]],"date-time":"2025-07-07T00:00:00Z","timestamp":1751846400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"}],"funder":[{"name":"Division of Intramural Research"}],"content-domain":{"domain":["link.springer.com"],"crossmark-restriction":false},"short-container-title":["Sci Rep"],"abstract":"<jats:title>Abstract<\/jats:title>\n          <jats:p>Vaccines against coronavirus disease 2019 (COVID-19), caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), are highly effective in preventing severe disease but are less consistent in protecting against infection and transmission. Developing vaccines with enhanced immunogenicity that can provide protection in both the upper and lower respiratory tract (URT and LRT) is crucial. Mucosal immunization induces immunity at the site of initial infection, the respiratory tract, thereby preventing or mitigating infection. Here, we compared immune responses elicited by intramuscular mRNA vaccination alone with those elicited by intramuscular mRNA vaccination followed by intranasal administration of ChAdOx1 nCoV-19 vaccine in mice. Although both vaccination strategies induced strong systemic immunity, robust humoral and cellular mucosal immune responses, including spike-specific IgA and tissue-resident T cells, were only detected upon mucosal vaccination. Compared to unvaccinated animals, mucosal vaccination resulted in migration of T cells and macrophages into the nasal turbinates, as well as migration and proliferation of B and T cells in the nasal-associated lymphoid tissue. While both vaccination regimens provided protection across the entire respiratory tract at 2 weeks post-vaccination, at 12 weeks post-vaccination, only the mice that received a mucosal vaccination remained protected in the URT. Gene-expression profiling of the respiratory tract at 2 days post-infection revealed distinct clustering between groups. Enrichment of immune signaling pathways, including B and T cells receptor pathways, was significantly higher in intranasally vaccinated animals. Together, our study demonstrates that mucosal vaccination provides durable protection against SARS-CoV-2 than intramuscular vaccination alone.<\/jats:p>","DOI":"10.1038\/s41598-025-06880-3","type":"journal-article","created":{"date-parts":[[2025,7,7]],"date-time":"2025-07-07T09:59:37Z","timestamp":1751882377000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":13,"title":["Intranasal booster induces durable mucosal immunity against SARS-CoV-2 in mice"],"prefix":"10.1038","volume":"15","author":[{"given":"Reshma","family":"Koolaparambil Mukesh","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tom","family":"Hill","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Franziska","family":"Kaiser","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jessica","family":"Prado-Smith","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jonathan E.","family":"Schulz","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shane","family":"Gallogly","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lisa","family":"Herbold","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kaitlyn","family":"Bauer","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Brian J.","family":"Smith","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lara","family":"Myers","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Aaron B.","family":"Carmody","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Carl","family":"Shaia","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Vincent J.","family":"Munster","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Neeltje","family":"van Doremalen","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2025,7,7]]},"reference":[{"key":"6880_CR1","unstructured":"WHO. WHO COVID-19 dashboard https:\/\/data.who.int\/dashboards\/covid19\/deaths?n=o. Accessed 05 Dec 2024."},{"key":"6880_CR2","unstructured":"FDA. FDA, FDA Approves First COVID-19 Vaccine, 2021, https:\/\/www.fda.gov\/news-events\/press-announcements\/fda-approves-first-covid-19-vaccine."},{"key":"6880_CR3","first-page":"1770","volume":"26","author":"YZ Huang","year":"2022","unstructured":"Huang, Y. Z. & Kuan, C. C. Vaccination to reduce severe COVID-19 and mortality in COVID-19 patients: A systematic review and meta-analysis. Eur. Rev. Med. Pharmacol. Sci. 26, 1770\u20131776 (2022).","journal-title":"Eur. Rev. Med. Pharmacol. Sci."},{"key":"6880_CR4","doi-asserted-by":"publisher","first-page":"567","DOI":"10.1038\/s41586-020-2622-0","volume":"586","author":"KS Corbett","year":"2020","unstructured":"Corbett, K. S. et al. SARS-CoV-2 mRNA vaccine design enabled by prototype pathogen preparedness. Nature 586, 567\u2013571 (2020).","journal-title":"Nature"},{"key":"6880_CR5","doi-asserted-by":"publisher","first-page":"467","DOI":"10.1016\/S0140-6736(20)31604-4","volume":"396","author":"PM Folegatti","year":"2020","unstructured":"Folegatti, P. M. et al. Safety and immunogenicity of the ChAdOx1 nCoV-19 vaccine against SARS-CoV-2: A preliminary report of a phase 1\/2, single-blind, randomised controlled trial. The Lancet 396, 467\u2013478 (2020).","journal-title":"The Lancet"},{"key":"6880_CR6","doi-asserted-by":"publisher","first-page":"531","DOI":"10.1056\/NEJMoa2116185","volume":"386","author":"LM Dunkle","year":"2022","unstructured":"Dunkle, L. M. et al. Efficacy and safety of NVX-CoV2373 in adults in the United States and Mexico. N. Engl. J. Med. 386, 531\u2013543 (2022).","journal-title":"N. Engl. J. Med."},{"key":"6880_CR7","doi-asserted-by":"publisher","first-page":"403","DOI":"10.1056\/NEJMoa2035389","volume":"384","author":"LR Baden","year":"2021","unstructured":"Baden, L. R. et al. Efficacy and safety of the mRNA-1273 SARS-CoV-2 vaccine. N. Engl. J. Med. 384, 403\u2013416 (2021).","journal-title":"N. Engl. J. Med."},{"key":"6880_CR8","doi-asserted-by":"publisher","first-page":"2603","DOI":"10.1056\/NEJMoa2034577","volume":"383","author":"FP Polack","year":"2020","unstructured":"Polack, F. P. et al. Safety and efficacy of the BNT162b2 mRNA Covid-19 vaccine. N. Engl. J. Med. 383, 2603\u20132615 (2020).","journal-title":"N. Engl. J. Med."},{"key":"6880_CR9","doi-asserted-by":"publisher","first-page":"1027271","DOI":"10.3389\/fmicb.2022.1027271","volume":"13","author":"J Dingemans","year":"2022","unstructured":"Dingemans, J. et al. Investigating SARS-CoV-2 breakthrough infections per variant and vaccine type. Front. Microbiol. 13, 1027271 (2022).","journal-title":"Front. Microbiol."},{"key":"6880_CR10","doi-asserted-by":"publisher","first-page":"54","DOI":"10.3390\/vaccines10010054","volume":"10","author":"P Kale","year":"2021","unstructured":"Kale, P. et al. Vaccine breakthrough infections by SARS-CoV-2 variants after ChAdOx1 nCoV-19 vaccination in healthcare workers. Vaccines (Basel) 10, 54 (2021).","journal-title":"Vaccines (Basel)"},{"key":"6880_CR11","doi-asserted-by":"publisher","first-page":"183","DOI":"10.1016\/S1473-3099(21)00648-4","volume":"22","author":"A Singanayagam","year":"2022","unstructured":"Singanayagam, A. et al. Community transmission and viral load kinetics of the SARS-CoV-2 delta (B. 1.617. 2) variant in vaccinated and unvaccinated individuals in the UK: A prospective, longitudinal, cohort study. Lancet Infect. Dis. 22, 183\u2013195 (2022).","journal-title":"Lancet Infect. Dis."},{"key":"6880_CR12","doi-asserted-by":"publisher","first-page":"104402","DOI":"10.1016\/j.ebiom.2022.104402","volume":"87","author":"F Liew","year":"2023","unstructured":"Liew, F. et al. SARS-CoV-2-specific nasal IgA wanes 9 months after hospitalisation with COVID-19 and is not induced by subsequent vaccination. EBioMedicine 87, 104402 (2023).","journal-title":"EBioMedicine"},{"key":"6880_CR13","doi-asserted-by":"publisher","first-page":"eadp8920","DOI":"10.1126\/scitranslmed.adp8920","volume":"16","author":"N Lasrado","year":"2024","unstructured":"Lasrado, N. et al. SARS-CoV-2 XBB.1.5 mRNA booster vaccination elicits limited mucosal immunity. Sci. Transl. Med. 16, eadp8920 (2024).","journal-title":"Sci. Transl. Med."},{"key":"6880_CR14","doi-asserted-by":"publisher","first-page":"eadd4853","DOI":"10.1126\/sciimmunol.add4853","volume":"7","author":"J Tang","year":"2022","unstructured":"Tang, J. et al. Respiratory mucosal immunity against SARS-CoV-2 after mRNA vaccination. Sci. Immunol. 7, eadd4853 (2022).","journal-title":"Sci. Immunol."},{"key":"6880_CR15","doi-asserted-by":"publisher","first-page":"936","DOI":"10.1002\/eji.202249823","volume":"52","author":"M Cokari\u0107 Brdov\u010dak","year":"2022","unstructured":"Cokari\u0107 Brdov\u010dak, M. et al. ChAdOx1-S adenoviral vector vaccine applied intranasally elicits superior mucosal immunity compared to the intramuscular route of vaccination. Eur. J. Immunol. 52, 936\u2013945 (2022).","journal-title":"Eur. J. Immunol."},{"key":"6880_CR16","doi-asserted-by":"publisher","first-page":"4207","DOI":"10.1038\/s41467-020-18077-5","volume":"11","author":"L Feng","year":"2020","unstructured":"Feng, L. et al. An adenovirus-vectored COVID-19 vaccine confers protection from SARS-COV-2 challenge in rhesus macaques. Nat. Commun. 11, 4207 (2020).","journal-title":"Nat. Commun."},{"key":"6880_CR17","doi-asserted-by":"publisher","first-page":"eabn6868","DOI":"10.1126\/scitranslmed.abn6868","volume":"14","author":"SN Langel","year":"2022","unstructured":"Langel, S. N. et al. Adenovirus type 5 SARS-CoV-2 vaccines delivered orally or intranasally reduced disease severity and transmission in a hamster model. Sci. Transl. Med. 14, eabn6868 (2022).","journal-title":"Sci. Transl. Med."},{"key":"6880_CR18","doi-asserted-by":"publisher","first-page":"eabh0755","DOI":"10.1126\/scitranslmed.abh0755","volume":"13","author":"N van Doremalen","year":"2021","unstructured":"van Doremalen, N. et al. Intranasal ChAdOx1 nCoV-19\/AZD1222 vaccination reduces viral shedding after SARS-CoV-2 D614G challenge in preclinical models. Sci. Transl. Med. 13, eabh0755 (2021).","journal-title":"Sci. Transl. Med."},{"key":"6880_CR19","doi-asserted-by":"publisher","first-page":"eadp1290","DOI":"10.1126\/sciadv.adp1290","volume":"10","author":"TL Darling","year":"2024","unstructured":"Darling, T. L. et al. Mucosal immunization with ChAd-SARS-CoV-2-S prevents sequential transmission of SARS-CoV-2 to unvaccinated hamsters. Sci. Adv. 10, eadp1290 (2024).","journal-title":"Sci. Adv."},{"key":"6880_CR20","doi-asserted-by":"publisher","first-page":"103788","DOI":"10.1016\/j.ebiom.2021.103788","volume":"75","author":"L Azzi","year":"2022","unstructured":"Azzi, L. et al. Mucosal immune response in BNT162b2 COVID-19 vaccine recipients. EBioMedicine 75, 103788 (2022).","journal-title":"EBioMedicine"},{"key":"6880_CR21","doi-asserted-by":"publisher","first-page":"e2310650","DOI":"10.1001\/jamanetworkopen.2023.10650","volume":"6","author":"F Menegale","year":"2023","unstructured":"Menegale, F. et al. Evaluation of waning of SARS-CoV-2 vaccine-induced immunity: A systematic review and meta-analysis. JAMA Netw. Open 6, e2310650\u2013e2310650 (2023).","journal-title":"JAMA Netw. Open"},{"key":"6880_CR22","doi-asserted-by":"crossref","unstructured":"L. J. Abu-Raddad, H. Chemaitelly, R. Bertollini, C.-V (2022) National Study Group for, Waning mRNA-1273 Vaccine Effectiveness against SARS-CoV-2 Infection in Qatar. N Engl J Med 386, 1091\u20131093","DOI":"10.1056\/NEJMc2119432"},{"key":"6880_CR23","doi-asserted-by":"publisher","first-page":"11467","DOI":"10.1038\/s41598-024-61922-6","volume":"14","author":"MA Haq","year":"2024","unstructured":"Haq, M. A. et al. Antibody longevity and waning following COVID-19 vaccination in a 1-year longitudinal cohort in Bangladesh. Sci. Rep. 14, 11467 (2024).","journal-title":"Sci. Rep."},{"key":"6880_CR24","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0104824","volume":"9","author":"MV Sanchez","year":"2014","unstructured":"Sanchez, M. V. et al. Intranasal delivery of influenza rNP adjuvanted with c-di-AMP induces strong humoral and cellular immune responses and provides protection against virus challenge. PLoS ONE 9, e104824 (2014).","journal-title":"PLoS ONE"},{"key":"6880_CR25","doi-asserted-by":"publisher","first-page":"183","DOI":"10.1186\/1743-422X-10-183","volume":"10","author":"YH Fu","year":"2013","unstructured":"Fu, Y. H. et al. Intranasal immunization with a helper-dependent adenoviral vector expressing the codon-optimized fusion glycoprotein of human respiratory syncytial virus elicits protective immunity in BALB\/c mice. Virol. J. 10, 183 (2013).","journal-title":"Virol. J."},{"key":"6880_CR26","doi-asserted-by":"publisher","first-page":"6193","DOI":"10.1038\/s41467-024-50133-2","volume":"15","author":"A Leekha","year":"2024","unstructured":"Leekha, A. et al. Multi-antigen intranasal vaccine protects against challenge with sarbecoviruses and prevents transmission in hamsters. Nat. Commun. 15, 6193 (2024).","journal-title":"Nat. Commun."},{"key":"6880_CR27","doi-asserted-by":"publisher","first-page":"537","DOI":"10.1038\/s41590-024-01743-x","volume":"25","author":"B Ying","year":"2024","unstructured":"Ying, B. et al. Mucosal vaccine-induced cross-reactive CD8+T cells protect against SARS-CoV-2 XBB.1.5 respiratory tract infection. Nat. Immunol. 25, 537\u2013551 (2024).","journal-title":"Nat. Immunol."},{"key":"6880_CR28","doi-asserted-by":"publisher","first-page":"22","DOI":"10.1111\/j.0105-2896.2005.00299.x","volume":"206","author":"J Bienenstock","year":"2005","unstructured":"Bienenstock, J. & McDermott, M. R. Bronchus-and nasal-associated lymphoid tissues. Immunol. Rev. 206, 22\u201331 (2005).","journal-title":"Immunol. Rev."},{"key":"6880_CR29","doi-asserted-by":"publisher","first-page":"1181991","DOI":"10.3389\/fimmu.2023.1181991","volume":"14","author":"R Patil","year":"2023","unstructured":"Patil, R., Palkar, S., Mishra, A., Patil, R. & Arankalle, V. Variable neutralizing antibody responses to 10 SARS-CoV-2 variants in natural infection with wild- type (B.1) virus, Kappa (B.1.617.1), and Delta (B.1.617.2) variants and COVISHIELD vaccine immunization in India: Utility of the MSD platform. Front. Immunol. 14, 1181991 (2023).","journal-title":"Front. Immunol."},{"key":"6880_CR30","doi-asserted-by":"publisher","first-page":"921","DOI":"10.1038\/s41586-024-08315-x","volume":"637","author":"F Jian","year":"2024","unstructured":"Jian, F. et al. Evolving antibody response to SARS-CoV-2 antigenic shift from XBB to JN.1. Nature 637, 921 (2024).","journal-title":"Nature"},{"key":"6880_CR31","doi-asserted-by":"publisher","first-page":"6903","DOI":"10.4049\/jimmunol.0900324","volume":"183","author":"TM Garcia-Bates","year":"2009","unstructured":"Garcia-Bates, T. M. et al. Peroxisome proliferator-activated receptor gamma ligands enhance human B cell antibody production and differentiation. J. Immunol. 183, 6903\u20136912 (2009).","journal-title":"J. Immunol."},{"key":"6880_CR32","doi-asserted-by":"publisher","first-page":"82","DOI":"10.1186\/s43141-021-00179-2","volume":"19","author":"AF AbdelMassih","year":"2021","unstructured":"AbdelMassih, A. F. et al. PPAR agonists as effective adjuvants for COVID-19 vaccines, by modifying immunogenetics: A review of literature. J. Genet. Eng. Biotechnol. 19, 82 (2021).","journal-title":"J. Genet. Eng. Biotechnol."},{"key":"6880_CR33","doi-asserted-by":"publisher","first-page":"1379","DOI":"10.1016\/j.immuni.2016.05.006","volume":"44","author":"J Zhao","year":"2016","unstructured":"Zhao, J. et al. Airway memory CD4+ T cells mediate protective immunity against emerging respiratory coronaviruses. Immunity 44, 1379\u20131391 (2016).","journal-title":"Immunity"},{"key":"6880_CR34","doi-asserted-by":"publisher","first-page":"319","DOI":"10.1038\/s41587-021-01037-9","volume":"40","author":"J Loske","year":"2022","unstructured":"Loske, J. et al. Pre-activated antiviral innate immunity in the upper airways controls early SARS-CoV-2 infection in children. Nat. Biotechnol. 40, 319\u2013324 (2022).","journal-title":"Nat. Biotechnol."},{"key":"6880_CR35","doi-asserted-by":"publisher","first-page":"169","DOI":"10.1016\/j.cell.2020.08.026","volume":"183","author":"AO Hassan","year":"2020","unstructured":"Hassan, A. O. et al. A single-dose intranasal ChAd vaccine protects upper and lower respiratory tracts against SARS-CoV-2. Cell 183, 169-184 e113 (2020).","journal-title":"Cell"},{"key":"6880_CR36","doi-asserted-by":"publisher","first-page":"eabd2223","DOI":"10.1126\/scitranslmed.abd2223","volume":"13","author":"D Sterlin","year":"2021","unstructured":"Sterlin, D. et al. IgA dominates the early neutralizing antibody response to SARS-CoV-2. Sci. Transl. Med. 13, eabd2223 (2021).","journal-title":"Sci. Transl. Med."},{"key":"6880_CR37","doi-asserted-by":"publisher","first-page":"1333","DOI":"10.1056\/NEJMc2209651","volume":"387","author":"S Havervall","year":"2022","unstructured":"Havervall, S. et al. Anti-spike mucosal IgA protection against SARS-CoV-2 omicron infection. N. Engl. J. Med. 387, 1333\u20131336 (2022).","journal-title":"N. Engl. J. Med."},{"key":"6880_CR38","doi-asserted-by":"publisher","first-page":"1887","DOI":"10.1038\/s41467-023-37559-w","volume":"14","author":"DK Pieren","year":"2023","unstructured":"Pieren, D. K. et al. Limited induction of polyfunctional lung-resident memory T cells against SARS-CoV-2 by mRNA vaccination compared to infection. Nat. Commun. 14, 1887 (2023).","journal-title":"Nat. Commun."},{"key":"6880_CR39","doi-asserted-by":"publisher","first-page":"630","DOI":"10.1038\/s41586-020-03041-6","volume":"590","author":"K McMahan","year":"2021","unstructured":"McMahan, K. et al. Correlates of protection against SARS-CoV-2 in rhesus macaques. Nature 590, 630\u2013634 (2021).","journal-title":"Nature"},{"key":"6880_CR40","doi-asserted-by":"publisher","first-page":"e85832","DOI":"10.1172\/jci.insight.85832","volume":"1","author":"KD Zens","year":"2016","unstructured":"Zens, K. D., Chen, J. K. & Farber, D. L. Vaccine-generated lung tissue\u2013resident memory T cells provide heterosubtypic protection to influenza infection. JCI insight 1, e85832 (2016).","journal-title":"JCI insight"},{"key":"6880_CR41","doi-asserted-by":"publisher","first-page":"10224","DOI":"10.1038\/ncomms10224","volume":"6","author":"A Jozwik","year":"2015","unstructured":"Jozwik, A. et al. RSV-specific airway resident memory CD8+ T cells and differential disease severity after experimental human infection. Nat. Commun. 6, 10224 (2015).","journal-title":"Nat. Commun."},{"key":"6880_CR42","doi-asserted-by":"publisher","first-page":"1962","DOI":"10.4161\/hv.25458","volume":"9","author":"A Ainai","year":"2013","unstructured":"Ainai, A. et al. Intranasal vaccination with an inactivated whole influenza virus vaccine induces strong antibody responses in serum and nasal mucus of healthy adults. Hum. Vaccin. Immunother. 9, 1962\u20131970 (2013).","journal-title":"Hum. Vaccin. Immunother."},{"key":"6880_CR43","doi-asserted-by":"publisher","first-page":"714","DOI":"10.1016\/j.vaccine.2021.12.057","volume":"40","author":"YL Yang","year":"2022","unstructured":"Yang, Y. L., Kim, J., Jeong, Y. & Jang, Y. S. Intranasal immunization with a Middle East respiratory syndrome-coronavirus antigen conjugated to the M-cell targeting ligand Co4B enhances antigen-specific mucosal and systemic immunity and protects against infection. Vaccine 40, 714\u2013725 (2022).","journal-title":"Vaccine"},{"key":"6880_CR44","doi-asserted-by":"publisher","first-page":"103037","DOI":"10.1016\/j.isci.2021.103037","volume":"24","author":"X An","year":"2021","unstructured":"An, X. et al. Single-dose intranasal vaccination elicits systemic and mucosal immunity against SARS-CoV-2. iScience 24, 103037 (2021).","journal-title":"iScience"},{"key":"6880_CR45","doi-asserted-by":"publisher","first-page":"1890","DOI":"10.1080\/22221751.2022.2097479","volume":"11","author":"X Li","year":"2022","unstructured":"Li, X. et al. Combining intramuscular and intranasal homologous prime-boost with a chimpanzee adenovirus-based COVID-19 vaccine elicits potent humoral and cellular immune responses in mice. Emerg. Microbes Infect. 11, 1890\u20131899 (2022).","journal-title":"Emerg. Microbes Infect."},{"key":"6880_CR46","doi-asserted-by":"crossref","unstructured":"Y. Sui et al. Adjuvanted subunit intranasal vaccine prevents SARS-CoV-2 onward transmission in hamsters. bioRxiv (2024).","DOI":"10.1101\/2024.05.13.593816"},{"key":"6880_CR47","doi-asserted-by":"publisher","first-page":"385","DOI":"10.1038\/s41586-023-06951-3","volume":"626","author":"K McMahan","year":"2024","unstructured":"McMahan, K. et al. Mucosal boosting enhances vaccine protection against SARS-CoV-2 in macaques. Nature 626, 385\u2013391 (2024).","journal-title":"Nature"},{"key":"6880_CR48","doi-asserted-by":"publisher","first-page":"82","DOI":"10.1038\/34184","volume":"391","author":"C Jiang","year":"1998","unstructured":"Jiang, C., Ting, A. T. & Seed, B. PPAR-gamma agonists inhibit production of monocyte inflammatory cytokines. Nature 391, 82\u201386 (1998).","journal-title":"Nature"},{"key":"6880_CR49","doi-asserted-by":"publisher","first-page":"2857","DOI":"10.1002\/1521-4141(2001010)31:10<2857::AID-IMMU2857>3.0.CO;2-X","volume":"31","author":"P Gosset","year":"2001","unstructured":"Gosset, P. et al. Peroxisome proliferator-activated receptor gamma activators affect the maturation of human monocyte-derived dendritic cells. Eur. J. Immunol. 31, 2857\u20132865 (2001).","journal-title":"Eur. J. Immunol."},{"key":"6880_CR50","doi-asserted-by":"publisher","first-page":"1667","DOI":"10.1172\/JCI13202","volume":"108","author":"K Setoguchi","year":"2001","unstructured":"Setoguchi, K. et al. Peroxisome proliferator-activated receptor-gamma haploinsufficiency enhances B cell proliferative responses and exacerbates experimentally induced arthritis. J. Clin. Invest. 108, 1667\u20131675 (2001).","journal-title":"J. Clin. Invest."},{"key":"6880_CR51","doi-asserted-by":"publisher","first-page":"6838","DOI":"10.1074\/jbc.M106908200","volume":"277","author":"DC Jones","year":"2002","unstructured":"Jones, D. C., Ding, X. & Daynes, R. A. Nuclear receptor peroxisome proliferator-activated receptor alpha (PPARalpha) is expressed in resting murine lymphocytes. The PPARalpha in T and B lymphocytes is both transactivation and transrepression competent. J. Biol. Chem. 277, 6838\u20136845 (2002).","journal-title":"J. Biol. Chem."},{"key":"6880_CR52","doi-asserted-by":"publisher","first-page":"1098","DOI":"10.1002\/1521-4141(200104)31:4<1098::AID-IMMU1098>3.0.CO;2-I","volume":"31","author":"SG Harris","year":"2001","unstructured":"Harris, S. G. & Phipps, R. P. The nuclear receptor PPAR gamma is expressed by mouse T lymphocytes and PPAR gamma agonists induce apoptosis. Eur. J. Immunol. 31, 1098\u20131105 (2001).","journal-title":"Eur. J. Immunol."},{"key":"6880_CR53","doi-asserted-by":"publisher","first-page":"3973","DOI":"10.1074\/jbc.M105619200","volume":"277","author":"XY Yang","year":"2002","unstructured":"Yang, X. Y. et al. Interleukin (IL)-4 indirectly suppresses IL-2 production by human T lymphocytes via peroxisome proliferator-activated receptor gamma activated by macrophage-derived 12\/15-lipoxygenase ligands. J. Biol. Chem. 277, 3973\u20133978 (2002).","journal-title":"J. Biol. Chem."},{"key":"6880_CR54","doi-asserted-by":"publisher","first-page":"362","DOI":"10.1016\/j.actbio.2019.03.049","volume":"90","author":"Y-C Kye","year":"2019","unstructured":"Kye, Y.-C. et al. Intranasal immunization with pneumococcal surface protein A in the presence of nanoparticle forming polysorbitol transporter adjuvant induces protective immunity against the Streptococcus pneumoniae infection. Acta Biomater. 90, 362\u2013372 (2019).","journal-title":"Acta Biomater."},{"key":"6880_CR55","doi-asserted-by":"publisher","first-page":"379","DOI":"10.1038\/s41385-021-00461-z","volume":"15","author":"MZM Zheng","year":"2022","unstructured":"Zheng, M. Z. M. & Wakim, L. M. Tissue resident memory T cells in the respiratory tract. Mucosal Immunol. 15, 379\u2013388 (2022).","journal-title":"Mucosal Immunol."},{"key":"6880_CR56","doi-asserted-by":"publisher","first-page":"eaam6970","DOI":"10.1126\/sciimmunol.aam6970","volume":"2","author":"A Pizzolla","year":"2017","unstructured":"Pizzolla, A. et al. Resident memory CD8+ T cells in the upper respiratory tract prevent pulmonary influenza virus infection. Sci. Immunol. 2, eaam6970 (2017).","journal-title":"Sci. Immunol."},{"key":"6880_CR57","doi-asserted-by":"publisher","first-page":"1913","DOI":"10.1038\/s41590-024-01951-5","volume":"25","author":"M Gagne","year":"2024","unstructured":"Gagne, M. et al. Mucosal adenovirus vaccine boosting elicits IgA and durably prevents XBB.1.16 infection in nonhuman primates. Nat. Immunol. 25, 1913\u20131927 (2024).","journal-title":"Nat. Immunol."},{"key":"6880_CR58","doi-asserted-by":"publisher","first-page":"104298","DOI":"10.1016\/j.ebiom.2022.104298","volume":"85","author":"M Madhavan","year":"2022","unstructured":"Madhavan, M. et al. Tolerability and immunogenicity of an intranasally-administered adenovirus-vectored COVID-19 vaccine: An open-label partially-randomised ascending dose phase I trial. EBioMedicine 85, 104298 (2022).","journal-title":"EBioMedicine"},{"key":"6880_CR59","doi-asserted-by":"publisher","first-page":"252","DOI":"10.1080\/01926230600713475","volume":"34","author":"JR Harkema","year":"2006","unstructured":"Harkema, J. R., Carey, S. A. & Wagner, J. G. The nose revisited: A brief review of the comparative structure, function, and toxicologic pathology of the nasal epithelium. Toxicol. Pathol. 34, 252\u2013269 (2006).","journal-title":"Toxicol. Pathol."},{"key":"6880_CR60","doi-asserted-by":"publisher","first-page":"566","DOI":"10.2174\/156720112803529828","volume":"9","author":"S Gizurarson","year":"2012","unstructured":"Gizurarson, S. Anatomical and histological factors affecting intranasal drug and vaccine delivery. Curr. Drug Deliv. 9, 566\u2013582 (2012).","journal-title":"Curr. Drug Deliv."},{"key":"6880_CR61","doi-asserted-by":"publisher","first-page":"2000045","DOI":"10.2807\/1560-7917.ES.2020.25.3.2000045","volume":"25","author":"VM Corman","year":"2020","unstructured":"Corman, V. M. et al. Detection of 2019 novel coronavirus (2019-nCoV) by real-time RT-PCR. Eurosurveillance 25, 2000045 (2020).","journal-title":"Eurosurveillance"},{"key":"6880_CR62","unstructured":"B. Bioinformatics. (Babraham Bioinformatics. (FastQC.https:\/\/www.bioinformatics.babraham.ac.uk\/projects\/fastqc\/))."},{"key":"6880_CR63","unstructured":"B. institute. (Broad institute (https:\/\/broadinstitute.github.io\/picard\/))."},{"key":"6880_CR64","doi-asserted-by":"publisher","first-page":"1338","DOI":"10.12688\/f1000research.15931.1","volume":"7","author":"SW Wingett","year":"2018","unstructured":"Wingett, S. W. & Andrews, S. FastQ Screen: A tool for multi-genome mapping and quality control. F1000Res 7, 1338 (2018).","journal-title":"F1000Res"},{"key":"6880_CR65","doi-asserted-by":"publisher","first-page":"257","DOI":"10.1186\/s13059-019-1891-0","volume":"20","author":"DE Wood","year":"2019","unstructured":"Wood, D. E., Lu, J. & Langmead, B. Improved metagenomic analysis with Kraken 2. Genome Biol. 20, 257 (2019).","journal-title":"Genome Biol."},{"key":"6880_CR66","doi-asserted-by":"publisher","first-page":"2678","DOI":"10.1093\/bioinformatics\/bts503","volume":"28","author":"F Garcia-Alcalde","year":"2012","unstructured":"Garcia-Alcalde, F. et al. Qualimap: Evaluating next-generation sequencing alignment data. Bioinformatics 28, 2678\u20132679 (2012).","journal-title":"Bioinformatics"},{"key":"6880_CR67","doi-asserted-by":"publisher","first-page":"2184","DOI":"10.1093\/bioinformatics\/bts356","volume":"28","author":"L Wang","year":"2012","unstructured":"Wang, L., Wang, S. & Li, W. RSeQC: Quality control of RNA-seq experiments. Bioinformatics 28, 2184\u20132185 (2012).","journal-title":"Bioinformatics"},{"key":"6880_CR68","doi-asserted-by":"publisher","DOI":"10.14806\/ej.17.1.200","author":"M Martin","year":"2011","unstructured":"Martin, M. Cutadapt removes adapter sequences from high-throughput sequencing reads. EMBnetJ https:\/\/doi.org\/10.14806\/ej.17.1.200 (2011).","journal-title":"EMBnetJ"},{"key":"6880_CR69","doi-asserted-by":"publisher","first-page":"15","DOI":"10.1093\/bioinformatics\/bts635","volume":"29","author":"A Dobin","year":"2013","unstructured":"Dobin, A. et al. STAR: Ultrafast universal RNA-seq aligner. Bioinformatics 29, 15\u201321 (2013).","journal-title":"Bioinformatics"},{"key":"6880_CR70","doi-asserted-by":"publisher","first-page":"323","DOI":"10.1186\/1471-2105-12-323","volume":"12","author":"B Li","year":"2011","unstructured":"Li, B. & Dewey, C. N. RSEM: Accurate transcript quantification from RNA-Seq data with or without a reference genome. BMC Bioinform. 12, 323 (2011).","journal-title":"BMC Bioinform."}],"container-title":["Scientific Reports"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.nature.com\/articles\/s41598-025-06880-3.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/www.nature.com\/articles\/s41598-025-06880-3","content-type":"text\/html","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/www.nature.com\/articles\/s41598-025-06880-3.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,7,7]],"date-time":"2025-07-07T11:03:35Z","timestamp":1751886215000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.nature.com\/articles\/s41598-025-06880-3"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2025,7,7]]},"references-count":70,"journal-issue":{"issue":"1","published-online":{"date-parts":[[2025,12]]}},"alternative-id":["6880"],"URL":"https:\/\/doi.org\/10.1038\/s41598-025-06880-3","relation":{},"ISSN":["2045-2322"],"issn-type":[{"value":"2045-2322","type":"electronic"}],"subject":[],"published":{"date-parts":[[2025,7,7]]},"assertion":[{"value":"18 March 2025","order":1,"name":"received","label":"Received","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"11 June 2025","order":2,"name":"accepted","label":"Accepted","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"7 July 2025","order":3,"name":"first_online","label":"First Online","group":{"name":"ArticleHistory","label":"Article History"}},{"order":1,"name":"Ethics","group":{"name":"EthicsHeading","label":"Declarations"}},{"value":"The authors declare no competing interests.","order":2,"name":"Ethics","group":{"name":"EthicsHeading","label":"Competing interests"}}],"article-number":"24224"}}