title: Contributions of the structural proteins of severe acute respiratory syndrome coronavirus to protective immunity.
abstract: 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.
authors.affiliation: Laboratory of Infectious Diseases, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD 20892-8007, USA. ubuchholz@niaid.nih.gov
authors.forename: Ursula J
authors.initials: UJ
authors.lastname: Buchholz
authors.forename: Alexander
authors.initials: A
authors.lastname: Bukreyev
authors.forename: Lijuan
authors.initials: L
authors.lastname: Yang
authors.forename: Elaine W
authors.initials: EW
authors.lastname: Lamirande
authors.forename: Brian R
authors.initials: BR
authors.lastname: Murphy
authors.forename: Kanta
authors.initials: K
authors.lastname: Subbarao
authors.forename: Peter L
authors.initials: PL
authors.lastname: Collins
mesh_terms: D000281:Administration, Intranasal; D000818:Animals; D000914:Antibodies, Viral / Q000276:immunology; D002460:Cell Line; D002522:Chlorocebus aethiops; D006224:Cricetinae; D004274:DNA, Recombinant / Q000235:genetics; D005822:Genetic Vectors / Q000235:genetics; D008562:Membrane Glycoproteins / Q000235:genetics / Q000276:immunology; D009500:Neutralization Tests; D010224:Parainfluenza Virus 3, Human / Q000235:genetics; D012137:Respiratory System / Q000276:immunology / Q000821:virology; D045473:Severe acute respiratory syndrome-related coronavirus / Q000737:chemistry* / Q000235:genetics / Q000254:growth & development / Q000276:immunology*; D045169:Severe Acute Respiratory Syndrome / Q000276:immunology* / Q000517:prevention & control* / Q000821:virology; D064370:Spike Glycoprotein, Coronavirus; D014611:Vaccination; D014709:Vero Cells; D014759:Viral Envelope Proteins / Q000235:genetics / Q000276:immunology*; D014763:Viral Matrix Proteins / Q000235:genetics / Q000276:immunology; D014765:Viral Vaccines / Q000008:administration & dosage / Q000235:genetics / Q000276:immunology*; D014779:Virus Replication / Q000502:physiology
chemical_list: D000914:Antibodies, Viral; D004274:DNA, Recombinant; D008562:Membrane Glycoproteins; D064370:Spike Glycoprotein, Coronavirus; D014759:Viral Envelope Proteins; D014763:Viral Matrix Proteins; D014765:Viral Vaccines; C578557:spike glycoprotein, SARS-CoV