{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,11,2]],"date-time":"2026-11-02T18:42:20Z","timestamp":1793644940315,"version":"4.5.1"},"reference-count":33,"publisher":"American Association for the Advancement of Science (AAAS)","issue":"820","content-domain":{"domain":["www.science.org"],"crossmark-restriction":true},"short-container-title":["Sci. Transl. Med."],"published-print":{"date-parts":[[2025,10,15]]},"abstract":"<jats:p>\n            The H5N1 clade 2.3.4.4b avian influenza virus outbreak in poultry and dairy cattle is a potential pandemic threat for humans. A safe and effective H5N1 influenza vaccine will be needed if the virus acquires the capacity for efficient human-to-human transmission and may also be useful as a veterinary vaccine. In this study, we demonstrate robust vaccine protection in a lethal model of H5N1 clade 2.3.4.4b influenza infection in cynomolgus macaques. We vaccinated 24 cynomolgus macaques with mRNA or rhesus adenovirus serotype 52 (RhAd52) vaccines expressing the hemagglutinin (HA) from H5N1 clade 2.3.4.4b by the intramuscular or intratracheal route and challenged them with the H5N1 human isolate hu-TX37-H5N1. Of sham control animals, 83% (five of six) developed severe rapidly progressive consolidative pneumonia and were euthanized by days 5 to 7 after challenge. In contrast, 100% (17 of 17) of vaccinated macaques survived and controlled virus replication to undetectable titers in both the upper and lower respiratory tracts by days 4 to 14 after challenge. Mucosal boosting with the RhAd52 HA vaccine generated robust mucosal antibody and T cell responses and afforded 6.3 and 5.1 log\n            <jats:sub>10<\/jats:sub>\n            median viral load reductions in viral RNA with no detectable infectious virus titers compared with sham controls in bronchoalveolar lavage and nasal swabs, respectively. These data demonstrate that an adenovirus-vectored vaccine can protect against lethal H5N1 clade 2.3.4.4b challenge in nonhuman primates and further highlight the importance of vaccine-elicited mucosal immunity.\n          <\/jats:p>","DOI":"10.1126\/scitranslmed.ady2282","type":"journal-article","created":{"date-parts":[[2025,10,15]],"date-time":"2025-10-15T17:58:27Z","timestamp":1760551107000},"update-policy":"https:\/\/doi.org\/10.34133\/aaas_crossmark","source":"Crossref","is-referenced-by-count":11,"title":["An intramuscular prime and mucosal boost vaccine regimen protects against lethal clade 2.3.4.4b H5N1 challenge in cynomolgus macaques"],"prefix":"10.1126","volume":"17","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-6762-2654","authenticated-orcid":true,"given":"Ninaad","family":"Lasrado","sequence":"first","affiliation":[{"name":"Center for Virology and Vaccine Research, Beth Israel Deaconess Medical Center, Boston, MA 02215, USA."},{"name":"Harvard Medical School, Boston, MA 02115, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9562-4603","authenticated-orcid":true,"given":"Liping","family":"Wang","sequence":"additional","affiliation":[{"name":"Center for Virology and Vaccine Research, Beth Israel Deaconess Medical Center, Boston, MA 02215, USA."},{"name":"Harvard Medical School, Boston, MA 02115, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0504-2181","authenticated-orcid":true,"given":"Jinyan","family":"Liu","sequence":"additional","affiliation":[{"name":"Center for Virology and Vaccine Research, Beth Israel Deaconess Medical Center, Boston, MA 02215, USA."},{"name":"Harvard Medical School, Boston, MA 02115, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5298-0288","authenticated-orcid":true,"given":"Annika","family":"R\u00f6ssler","sequence":"additional","affiliation":[{"name":"Center for Virology and Vaccine Research, Beth Israel Deaconess Medical Center, Boston, MA 02215, USA."},{"name":"Harvard Medical School, Boston, MA 02115, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1864-562X","authenticated-orcid":true,"given":"Jayeshbhai","family":"Chaudhari","sequence":"additional","affiliation":[{"name":"Center for Virology and Vaccine Research, Beth Israel Deaconess Medical Center, Boston, MA 02215, USA."},{"name":"Harvard Medical School, Boston, MA 02115, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9051-8388","authenticated-orcid":true,"given":"Qixin","family":"Wang","sequence":"additional","affiliation":[{"name":"Department of Immunology and Infectious Diseases, Harvard T.H. Chan School of Public Health, Boston, MA 02115, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2632-1948","authenticated-orcid":true,"given":"Jonathon J.","family":"Stone","sequence":"additional","affiliation":[{"name":"Tufts University Cummings School of Veterinary Medicine, North Grafton, MA 01536, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Francisco Armando","family":"Granados-Contreras","sequence":"additional","affiliation":[{"name":"Center for Virology and Vaccine Research, Beth Israel Deaconess Medical Center, Boston, MA 02215, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jessica","family":"Wu","sequence":"additional","affiliation":[{"name":"Center for Virology and Vaccine Research, Beth Israel Deaconess Medical Center, Boston, MA 02215, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3242-5874","authenticated-orcid":true,"given":"Dalia N.","family":"Cabrera-Barragan","sequence":"additional","affiliation":[{"name":"Center for Virology and Vaccine Research, Beth Israel Deaconess Medical Center, Boston, MA 02215, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8046-5638","authenticated-orcid":true,"given":"Alejandra","family":"Waller-Pulido","sequence":"additional","affiliation":[{"name":"Center for Virology and Vaccine Research, Beth Israel Deaconess Medical Center, Boston, MA 02215, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0002-2318-4933","authenticated-orcid":true,"given":"Samuel J.","family":"Nangle","sequence":"additional","affiliation":[{"name":"Center for Virology and Vaccine Research, Beth Israel Deaconess Medical Center, Boston, MA 02215, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Krishna","family":"Shah","sequence":"additional","affiliation":[{"name":"Center for Virology and Vaccine Research, Beth Israel Deaconess Medical Center, Boston, MA 02215, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Reed","family":"Boduch","sequence":"additional","affiliation":[{"name":"Center for Virology and Vaccine Research, Beth Israel Deaconess Medical Center, Boston, MA 02215, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Siddhesh","family":"Warke","sequence":"additional","affiliation":[{"name":"Center for Virology and Vaccine Research, Beth Israel Deaconess Medical Center, Boston, MA 02215, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0001-5524-8703","authenticated-orcid":true,"given":"Anthony","family":"Cook","sequence":"additional","affiliation":[{"name":"Bioqual Inc., Rockville, MD 20850, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0002-6711-2384","authenticated-orcid":true,"given":"Christopher","family":"Kitajewski","sequence":"additional","affiliation":[{"name":"Bioqual Inc., Rockville, MD 20850, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2126-3008","authenticated-orcid":true,"given":"Laurent","family":"Pessaint","sequence":"additional","affiliation":[{"name":"Bioqual Inc., Rockville, MD 20850, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7852-0135","authenticated-orcid":true,"given":"Mark G.","family":"Lewis","sequence":"additional","affiliation":[{"name":"Bioqual Inc., Rockville, MD 20850, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1103-9608","authenticated-orcid":true,"given":"Hanne","family":"Andersen","sequence":"additional","affiliation":[{"name":"Bioqual Inc., Rockville, MD 20850, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6237-6191","authenticated-orcid":true,"given":"Amanda J.","family":"Martinot","sequence":"additional","affiliation":[{"name":"Tufts University Cummings School of Veterinary Medicine, North Grafton, MA 01536, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8866-3532","authenticated-orcid":true,"given":"Ryan P.","family":"McNamara","sequence":"additional","affiliation":[{"name":"Department of Immunology and Infectious Diseases, Harvard T.H. Chan School of Public Health, Boston, MA 02115, USA."},{"name":"Ragon Institute of Mass General, MIT, and Harvard, Cambridge MA 02139, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5127-4659","authenticated-orcid":true,"given":"Dan H.","family":"Barouch","sequence":"additional","affiliation":[{"name":"Center for Virology and Vaccine Research, Beth Israel Deaconess Medical Center, Boston, MA 02215, USA."},{"name":"Harvard Medical School, Boston, MA 02115, USA."},{"name":"Ragon Institute of Mass General, MIT, and Harvard, Cambridge MA 02139, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"221","reference":[{"key":"e_1_3_2_2_2","unstructured":"National Emerging Special Pathogens Training & Education Center Situation report: Highly pathogenic avian influenza A (H5N1) (NETEC 30 January 2023)."},{"key":"e_1_3_2_3_2","unstructured":"World Health Organization Cumulative number of confirmed human cases for avian influenza A(H5N1) reported to WHO 2003\u20132023 (World Health Organization 14 July 2023)."},{"key":"e_1_3_2_4_2","doi-asserted-by":"publisher","DOI":"10.1038\/s41586-024-08054-z"},{"key":"e_1_3_2_5_2","doi-asserted-by":"publisher","DOI":"10.1080\/22221751.2021.1872355"},{"key":"e_1_3_2_6_2","unstructured":"US Centers for Disease Control H5 bird flu: Current situation (US Centers for Disease Control 2025)."},{"key":"e_1_3_2_7_2","doi-asserted-by":"publisher","DOI":"10.3201\/eid3007.240717"},{"key":"e_1_3_2_8_2","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMoa2414610"},{"key":"e_1_3_2_9_2","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMc2405371"},{"key":"e_1_3_2_10_2","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMc2407264"},{"key":"e_1_3_2_11_2","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMc2415890"},{"key":"e_1_3_2_12_2","unstructured":"US Centers for Disease Control First H5 bird flu death reported in United States (US Centers for Disease Control 2025)."},{"key":"e_1_3_2_13_2","doi-asserted-by":"publisher","DOI":"10.1038\/s41591-024-03256-4"},{"key":"e_1_3_2_14_2","doi-asserted-by":"publisher","DOI":"10.1038\/s41586-023-06951-3"},{"key":"e_1_3_2_15_2","doi-asserted-by":"publisher","DOI":"10.1038\/s41590-024-01951-5"},{"key":"e_1_3_2_16_2","doi-asserted-by":"publisher","DOI":"10.1128\/JVI.00974-21"},{"key":"e_1_3_2_17_2","doi-asserted-by":"publisher","DOI":"10.1128\/JVI.00159-18"},{"key":"e_1_3_2_18_2","doi-asserted-by":"publisher","DOI":"10.1126\/science.aah6157"},{"key":"e_1_3_2_19_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.immuni.2025.07.020"},{"key":"e_1_3_2_20_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.isci.2024.110174"},{"key":"e_1_3_2_21_2","doi-asserted-by":"publisher","DOI":"10.1038\/s41586-024-07849-4"},{"key":"e_1_3_2_22_2","doi-asserted-by":"publisher","DOI":"10.3201\/eid3007.240508"},{"key":"e_1_3_2_23_2","doi-asserted-by":"publisher","DOI":"10.1038\/s41467-024-55546-7"},{"key":"e_1_3_2_24_2","doi-asserted-by":"publisher","DOI":"10.1038\/s41467-024-48555-z"},{"key":"e_1_3_2_25_2","doi-asserted-by":"publisher","DOI":"10.1126\/scitranslmed.ads1273"},{"key":"e_1_3_2_26_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.ymthe.2024.12.032"},{"key":"e_1_3_2_27_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.jcf.2015.04.003"},{"key":"e_1_3_2_28_2","doi-asserted-by":"publisher","DOI":"10.1038\/s41591-024-03189-y"},{"key":"e_1_3_2_29_2","doi-asserted-by":"publisher","DOI":"10.1038\/s41591-025-03599-6"},{"key":"e_1_3_2_30_2","doi-asserted-by":"publisher","DOI":"10.1126\/scitranslmed.adu7646"},{"key":"e_1_3_2_31_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.isci.2025.112721"},{"key":"e_1_3_2_32_2","doi-asserted-by":"publisher","DOI":"10.1126\/scitranslmed.adp8920"},{"key":"e_1_3_2_33_2","doi-asserted-by":"publisher","DOI":"10.1128\/JVI.02696-06"},{"key":"e_1_3_2_34_2","first-page":"493","article-title":"A simple method of estimating fifty per cent endpoints","volume":"27","author":"Reed L. J.","year":"1938","unstructured":"L. J. Reed, H. Muench, A simple method of estimating fifty per cent endpoints. Am. J. Hyg. 27, 493\u2013495 (1938).","journal-title":"Am. J. Hyg."}],"container-title":["Science Translational Medicine"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.science.org\/doi\/pdf\/10.1126\/scitranslmed.ady2282","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,15]],"date-time":"2025-10-15T17:58:29Z","timestamp":1760551109000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.science.org\/doi\/10.1126\/scitranslmed.ady2282"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2025,10,15]]},"references-count":33,"journal-issue":{"issue":"820","published-print":{"date-parts":[[2025,10,15]]}},"alternative-id":["10.1126\/scitranslmed.ady2282"],"URL":"https:\/\/doi.org\/10.1126\/scitranslmed.ady2282","relation":{},"ISSN":["1946-6234","1946-6242"],"issn-type":[{"value":"1946-6234","type":"print"},{"value":"1946-6242","type":"electronic"}],"subject":[],"published":{"date-parts":[[2025,10,15]]},"assertion":[{"value":"2025-04-14","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2025-07-04","order":1,"name":"revised","label":"Revised","group":{"name":"publication_history","label":"Publication History"}},{"value":"2025-08-06","order":2,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2025-10-15","order":3,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}],"article-number":"eady2282"}}