{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,11,3]],"date-time":"2026-11-03T03:51:15Z","timestamp":1793677875874,"version":"4.5.1"},"reference-count":40,"publisher":"American Association for the Advancement of Science (AAAS)","issue":"835","funder":[{"name":"Leyden Laboratories B.V."}],"content-domain":{"domain":["www.science.org"],"crossmark-restriction":true},"short-container-title":["Sci. Transl. Med."],"published-print":{"date-parts":[[2026,2,4]]},"abstract":"<jats:p>Systemic administration of influenza virus\u2013specific monoclonal antibodies achieves low concentrations in the nasal mucosa, the portal of infection. Intranasal administration may be more relevant for preventing infection, but the pharmacokinetics of intranasal influenza antibodies is unknown. We present results of preclinical studies and first-in-human phase 1 trials of the intranasally administered CR9114, an anti\u2013hemagglutinin stem antibody that protects against influenza A and B viruses. We tested safety and tolerability of different schedules and doses; pharmacokinetics in nasal mucosal lining fluid of the nose and nasopharynx, saliva, and serum; and ex vivo functionality. We evaluated in vivo efficacy of CR9114 in mice and nonhuman primates. Intranasal CR9114 was safe and well tolerated across all doses and schedules. The half-life of CR9114 in the nose was ~3 hours. Steady-state concentrations were rapidly attained and sustained with multidosing. Trough concentrations were up to 92-fold higher with twice-daily administration compared with once-daily administration. Pharmacokinetics of intranasal CR9114 in nonhuman primates mirrored that of humans better than mice. Postdose nasal samples potently bound hemagglutinin from diverse strains of influenza A and B viruses and, particularly at the 10-milligram dose, neutralized A\/H1N1, A\/H5N1, and A\/H3N2 more potently than baseline samples. Twice-daily administration of CR9114 protected nonhuman primates against influenza virus challenge with the same intranasal formulation and device as used in humans, providing evidence for the efficacy of intranasal multidosing. Together, these study findings characterize the pharmacokinetics of CR9114 after intranasal administration and provide proof of concept that intranasal antibodies can elicit efficacious passive immunity against influenza viruses.<\/jats:p>","DOI":"10.1126\/scitranslmed.adz1580","type":"journal-article","created":{"date-parts":[[2026,2,4]],"date-time":"2026-02-04T18:58:12Z","timestamp":1770231492000},"update-policy":"https:\/\/doi.org\/10.34133\/aaas_crossmark","source":"Crossref","is-referenced-by-count":7,"title":["Phase 1 and preclinical studies reveal safety, pharmacokinetics, and efficacy of intranasal delivery of the influenza antibody CR9114"],"prefix":"10.1126","volume":"18","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-1765-4890","authenticated-orcid":true,"given":"Anna L.","family":"Beukenhorst","sequence":"first","affiliation":[{"name":"Department of Epidemiology, Harvard T. H. Chan School of Public Health, Boston, MA 02115, USA."},{"name":"Leyden Laboratories, Leiden, 2333 BK, Netherlands."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Robin","family":"Rogiers","sequence":"additional","affiliation":[{"name":"Leyden Laboratories, Leiden, 2333 BK, Netherlands."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7403-261X","authenticated-orcid":true,"given":"Keira L.","family":"Rice","sequence":"additional","affiliation":[{"name":"Leyden Laboratories, Leiden, 2333 BK, Netherlands."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"George","family":"Booth","sequence":"additional","affiliation":[{"name":"Leyden Laboratories, Leiden, 2333 BK, Netherlands."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Joost","family":"Haasnoot","sequence":"additional","affiliation":[{"name":"Leyden Laboratories, Leiden, 2333 BK, Netherlands."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0678-9765","authenticated-orcid":true,"given":"Joseph","family":"Nkolola","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\/0009-0002-9360-8498","authenticated-orcid":true,"given":"Jose","family":"Ayala","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\/0000-0002-9562-4603","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."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4687-9626","authenticated-orcid":true,"given":"Boris","family":"Julg","sequence":"additional","affiliation":[{"name":"Leyden Laboratories, Leiden, 2333 BK, Netherlands."},{"name":"Ragon Institute of Mass General, MIT, and Harvard, Cambridge, MA 02139, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0006-7548-5251","authenticated-orcid":true,"given":"Andrea K.","family":"Pastini","sequence":"additional","affiliation":[{"name":"Leyden Laboratories, Leiden, 2333 BK, Netherlands."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Helene","family":"Vietsch","sequence":"additional","affiliation":[{"name":"Leyden Laboratories, Leiden, 2333 BK, Netherlands."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zolt\u00e1n","family":"Magyarics","sequence":"additional","affiliation":[{"name":"Leyden Laboratories, Leiden, 2333 BK, Netherlands."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Evmorfia","family":"Chatzifotiou","sequence":"additional","affiliation":[{"name":"Leyden Laboratories, Leiden, 2333 BK, Netherlands."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7978-3815","authenticated-orcid":true,"given":"Nigel","family":"Temperton","sequence":"additional","affiliation":[{"name":"Viral Pseudotype Unit, Medway School of Pharmacy, University of Kent and University of Greenwich, Chatham, ME4 4TB, UK."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6352-3843","authenticated-orcid":true,"given":"Kelly A. S.","family":"da Costa","sequence":"additional","affiliation":[{"name":"Viral Pseudotype Unit, Medway School of Pharmacy, University of Kent and University of Greenwich, Chatham, ME4 4TB, UK."},{"name":"Division of Clinical Medicine, School of Medicine and Population, University of Sheffield, Sheffield, S1 4DT, UK."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Martin H.","family":"Koldijk","sequence":"additional","affiliation":[{"name":"Leyden Laboratories, Leiden, 2333 BK, Netherlands."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Justin","family":"Crawford","sequence":"additional","affiliation":[{"name":"Leyden Laboratories, Leiden, 2333 BK, Netherlands."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sagrario Arias","family":"Rivas","sequence":"additional","affiliation":[{"name":"Leyden Laboratories, Leiden, 2333 BK, Netherlands."}],"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."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7424-6009","authenticated-orcid":true,"given":"Clarissa M.","family":"Koch","sequence":"additional","affiliation":[{"name":"Leyden Laboratories, Leiden, 2333 BK, Netherlands."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jaap","family":"Goudsmit","sequence":"additional","affiliation":[{"name":"Department of Epidemiology, Harvard T. 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