{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,3,24]],"date-time":"2026-03-24T09:48:35Z","timestamp":1774345715647,"version":"3.50.1"},"reference-count":19,"publisher":"Proceedings of the National Academy of Sciences","issue":"43","content-domain":{"domain":["www.pnas.org"],"crossmark-restriction":true},"short-container-title":["Proc. Natl. Acad. Sci. U.S.A."],"published-print":{"date-parts":[[2006,10,24]]},"abstract":"<jats:p>The remarkable infectivity and virulence of the 1918 influenza virus resulted in an unprecedented pandemic, raising the question of whether it is possible to develop protective immunity to this virus and whether immune evasion may have contributed to its spread. Here, we report that the highly lethal 1918 virus is susceptible to immune protection by a preventive vaccine, and we define its mechanism of action. Immunization with plasmid expression vectors encoding hemagglutinin (HA) elicited potent CD4 and CD8 cellular responses as well as neutralizing antibodies. Antibody specificity and titer were defined by a microneutralization and a pseudotype assay that could assess antibody specificity without the need for high-level biocontainment. This pseudotype inhibition assay can define evolving serotypes of influenza viruses and facilitate the development of immune sera and neutralizing monoclonal antibodies that may help contain pandemic influenza. Notably, mice vaccinated with 1918 HA plasmid DNAs showed complete protection to lethal challenge. T cell depletion had no effect on immunity, but passive transfer of purified IgG from anti-H1(1918) immunized mice provided protective immunity for na\u00efve mice challenged with infectious 1918 virus. Thus, humoral immunity directed at the viral HA can protect against the 1918 pandemic virus.<\/jats:p>","DOI":"10.1073\/pnas.0607564103","type":"journal-article","created":{"date-parts":[[2006,10,17]],"date-time":"2006-10-17T12:10:00Z","timestamp":1161087000000},"page":"15987-15991","update-policy":"https:\/\/doi.org\/10.1073\/pnas.cm10313","source":"Crossref","is-referenced-by-count":68,"title":["Protective immunity to lethal challenge of the 1918 pandemic influenza virus by vaccination"],"prefix":"10.1073","volume":"103","author":[{"given":"Wing-pui","family":"Kong","sequence":"first","affiliation":[{"name":"*Vaccine Research Center, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Room 4502, Building 40, MSC-3005, 40 Convent Drive, Bethesda, MD 20892-3005;"}]},{"given":"Chantelle","family":"Hood","sequence":"additional","affiliation":[{"name":"*Vaccine Research Center, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Room 4502, Building 40, MSC-3005, 40 Convent Drive, Bethesda, MD 20892-3005;"}]},{"given":"Zhi-yong","family":"Yang","sequence":"additional","affiliation":[{"name":"*Vaccine Research Center, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Room 4502, Building 40, MSC-3005, 40 Convent Drive, Bethesda, MD 20892-3005;"}]},{"given":"Chih-Jen","family":"Wei","sequence":"additional","affiliation":[{"name":"*Vaccine Research Center, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Room 4502, Building 40, MSC-3005, 40 Convent Drive, Bethesda, MD 20892-3005;"}]},{"given":"Ling","family":"Xu","sequence":"additional","affiliation":[{"name":"*Vaccine Research Center, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Room 4502, Building 40, MSC-3005, 40 Convent Drive, Bethesda, MD 20892-3005;"}]},{"given":"Adolfo","family":"Garc\u00eda-Sastre","sequence":"additional","affiliation":[{"name":"Department of Microbiology, Mount Sinai School of Medicine, One Gustave L. Levy Place, Box 1124, New York, NY 10029; and"}]},{"given":"Terrence M.","family":"Tumpey","sequence":"additional","affiliation":[{"name":"Influenza Branch, Mailstop G-16, Division of Viral and Rickettsial Diseases, National Center for Infectious Diseases, Centers for Disease Control and Prevention, 1600 Clifton Road Northeast, Atlanta, GA 30333"}]},{"given":"Gary J.","family":"Nabel","sequence":"additional","affiliation":[{"name":"*Vaccine Research Center, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Room 4502, Building 40, MSC-3005, 40 Convent Drive, Bethesda, MD 20892-3005;"}]}],"member":"341","published-online":{"date-parts":[[2006,10,24]]},"reference":[{"key":"e_1_3_3_1_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.jmb.2005.11.002"},{"key":"e_1_3_3_2_2","doi-asserted-by":"publisher","DOI":"10.1038\/nature04230"},{"key":"e_1_3_3_3_2","doi-asserted-by":"publisher","DOI":"10.1128\/JVI.79.17.11533-11536.2005"},{"key":"e_1_3_3_4_2","doi-asserted-by":"publisher","DOI":"10.1128\/JVI.78.22.12462-12470.2004"},{"key":"e_1_3_3_5_2","doi-asserted-by":"publisher","DOI":"10.1038\/nature02951"},{"key":"e_1_3_3_6_2","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.0308391100"},{"key":"e_1_3_3_7_2","doi-asserted-by":"publisher","DOI":"10.1126\/science.1093373"},{"key":"e_1_3_3_8_2","doi-asserted-by":"publisher","DOI":"10.1126\/science.1093155"},{"key":"e_1_3_3_9_2","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.031575198"},{"key":"e_1_3_3_10_2","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.100140097"},{"key":"e_1_3_3_11_2","doi-asserted-by":"publisher","DOI":"10.1126\/science.1119392"},{"key":"e_1_3_3_12_2","doi-asserted-by":"publisher","DOI":"10.1038\/nature02463"},{"key":"e_1_3_3_13_2","doi-asserted-by":"publisher","DOI":"10.1086\/314713"},{"key":"e_1_3_3_14_2","doi-asserted-by":"publisher","DOI":"10.1128\/JVI.77.23.12764-12772.2003"},{"key":"e_1_3_3_15_2","doi-asserted-by":"publisher","DOI":"10.1128\/JVI.79.14.8828-8834.2005"},{"key":"e_1_3_3_16_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.cell.2004.08.007"},{"key":"e_1_3_3_17_2","doi-asserted-by":"publisher","DOI":"10.1128\/JVI.78.8.4029-4036.2004"},{"key":"e_1_3_3_18_2","doi-asserted-by":"publisher","DOI":"10.1128\/JCM.37.4.937-943.1999"},{"key":"e_1_3_3_19_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.vaccine.2005.04.047"}],"container-title":["Proceedings of the National Academy of Sciences"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/pnas.org\/doi\/pdf\/10.1073\/pnas.0607564103","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2022,4,12]],"date-time":"2022-04-12T18:38:40Z","timestamp":1649788720000},"score":1,"resource":{"primary":{"URL":"https:\/\/pnas.org\/doi\/full\/10.1073\/pnas.0607564103"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2006,10,24]]},"references-count":19,"journal-issue":{"issue":"43","published-print":{"date-parts":[[2006,10,24]]}},"alternative-id":["10.1073\/pnas.0607564103"],"URL":"https:\/\/doi.org\/10.1073\/pnas.0607564103","relation":{},"ISSN":["0027-8424","1091-6490"],"issn-type":[{"value":"0027-8424","type":"print"},{"value":"1091-6490","type":"electronic"}],"subject":[],"published":{"date-parts":[[2006,10,24]]},"assertion":[{"value":"2006-05-16","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2006-10-24","order":2,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}]}}