{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,22]],"date-time":"2026-10-22T08:44:24Z","timestamp":1792658664562,"version":"4.5.0"},"reference-count":32,"publisher":"National Academy of Sciences","issue":"26","content-domain":{"domain":["www.pnas.org"],"crossmark-restriction":true},"short-container-title":["Proc. Natl. Acad. Sci. U.S.A."],"published-print":{"date-parts":[[2004,6,29]]},"abstract":"<jats:p>We investigated the contributions of the structural proteins of severe acute respiratory syndrome (SARS) coronavirus (CoV) to protective immunity by expressing them individually and in combinations from a recombinant parainfluenza virus (PIV) type 3 vector called BHPIV3. This vector provided direct immunization of the respiratory tract, the major site of SARS transmission, replication, and disease. The BHPIV3\/SARS recombinants were evaluated for immunogenicity and protective efficacy in hamsters, which support a high level of pulmonary SARS-CoV replication. A single intranasal administration of BHPIV3 expressing the SARS-CoV spike protein (S) induced a high titer of SARS-CoV-neutralizing serum antibodies, only 2-fold less than that induced by SARS-CoV infection. The expression of S with the two other putative virion envelope proteins, the matrix M and small envelope E proteins, did not augment the neutralizing antibody response. In absence of S, expression of M and E or the nucleocapsid protein N did not induce a detectable serum SARS-CoV-neutralizing antibody response. Immunization with BHPIV3 expressing S provided complete protection against SARS-CoV challenge in the lower respiratory tract and partial protection in the upper respiratory tract. This was augmented slightly by coexpression with M and E. Expression of M, E, or N in the absence of S did not confer detectable protection. These results identify S among the structural proteins as the only significant SARS-CoV neutralization antigen and protective antigen and show that a single mucosal immunization is highly protective in an experimental animal that supports efficient replication of SARS-CoV.<\/jats:p>","DOI":"10.1073\/pnas.0403492101","type":"journal-article","created":{"date-parts":[[2004,6,21]],"date-time":"2004-06-21T20:16:55Z","timestamp":1087849015000},"page":"9804-9809","update-policy":"https:\/\/doi.org\/10.1073\/pnas.cm10313","source":"Crossref","is-referenced-by-count":354,"title":["Contributions of the structural proteins of severe acute respiratory syndrome coronavirus to protective immunity"],"prefix":"10.1073","volume":"101","author":[{"given":"Ursula J.","family":"Buchholz","sequence":"first","affiliation":[{"name":"Laboratory of Infectious Diseases, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD 20892-8007"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alexander","family":"Bukreyev","sequence":"additional","affiliation":[{"name":"Laboratory of Infectious Diseases, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD 20892-8007"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lijuan","family":"Yang","sequence":"additional","affiliation":[{"name":"Laboratory of Infectious Diseases, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD 20892-8007"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Elaine W.","family":"Lamirande","sequence":"additional","affiliation":[{"name":"Laboratory of Infectious Diseases, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD 20892-8007"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Brian R.","family":"Murphy","sequence":"additional","affiliation":[{"name":"Laboratory of Infectious Diseases, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD 20892-8007"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kanta","family":"Subbarao","sequence":"additional","affiliation":[{"name":"Laboratory of Infectious Diseases, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD 20892-8007"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Peter L.","family":"Collins","sequence":"additional","affiliation":[{"name":"Laboratory of Infectious Diseases, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD 20892-8007"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"341","published-online":{"date-parts":[[2004,6,21]]},"reference":[{"key":"e_1_3_2_1_2","first-page":"81","volume":"78","year":"2003","unstructured":"World Health Organization (2003) Wkly. 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